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Washout Period (washout + period)
Kinds of Washout Period Selected AbstractsCombined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24-h intragastric pH in healthy volunteersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007V. NORRIS Summary Aim To compare antisecretory effects of rabeprazole and esomeprazole after single and repeat dosing in Helicobacter pylori -negative healthy volunteers. Methods Results were pooled from three smaller, open, crossover, randomized studies to obtain data from 80 subjects. The studies compared: (a) 5 days' dosing of 20 mg rabeprazole and esomeprazole (n = 24); (b) single doses of rabeprazole 20 mg and esomeprazole 40 mg (n = 27) and (c) 5 days' dosing of rabeprazole 10 mg and esomeprazole 20 mg (n = 29). Washout periods were ,14 days. Intragastric pH was recorded continuously for 24 h on days 0, 1 and 5. Results Single doses of rabeprazole 20 mg maintained 24-h intragastric pH >4 for longer than esomeprazole 20 mg (45% vs. 32%; P < 0.001); rabeprazole 20 mg and esomeprazole 40 mg were equivalent in their effects. After 5 days' dosing, rabeprazole 20 mg maintained pH >4 for longer than esomeprazole 20 mg (62% vs. 56%; P = 0.046); the reverse was true for esomeprazole 20 mg vs. rabeprazole 10 mg (56% vs. 48%; P = 0.035). In general, intragastric pH AUC during 0,5 h after dosing was higher after esomeprazole than rabeprazole, whereas the reverse was true during the night. Conclusions The order of effects on 24-h pH was: rabeprazole 10 mg , esomeprazole 20 mg < rabeprazole 20 mg = esomeprazole 40 mg. Esomeprazole acts faster, whereas rabeprazole's effect lasts longer. [source] Insulin pump therapy vs. multiple daily injections in obese Type 2 diabetic patientsDIABETIC MEDICINE, Issue 8 2005J. Wainstein Abstract Aims To compare the efficacy of insulin pump treatment with multiple daily injections in the treatment of poorly controlled obese Type 2 diabetic patients already receiving two or more daily injections of insulin plus metformin. Methods Forty obese Type 2 diabetic subjects (using insulin) were randomized to treatment with continuous subcutaneous infusion pump (CSII) (Minimed®) or multiple daily insulin injections (MDI). At the end of the first 18-week treatment period, patients underwent a 12-week washout period during which they were treated with MDI plus metformin. They were then crossed-over to the other treatment for an 18-week follow-up period. Patients performed 4-point daily self blood-glucose monitoring (SBGM) on a regular basis and 7-point monitoring prior to visits 2, 8, 10 and 16. A subset of patients underwent continuous glucose monitoring using the Minimed® continuous glucose monitoring system (CGMS) at visits 2, 8, 10 and 16. A standard meal test was performed in which serum glucose was tested at fasting and once each hour for 6 h following a test meal. Glucose levels were plotted against time and the area under the curve (AUC) was calculated. HbA1c, weight, daily insulin dose and hypoglycaemic episodes were recorded. Results In obese Type 2 diabetic patients already treated with insulin, treatment with CSII significantly reduced HbA1c levels compared with treatment with MDI. An additional CSII treatment benefit was demonstrated by reduced meal-test glucose AUC. Initial reduction of daily insulin requirement observed in CSII-treated subjects during the first treatment period was attributable to a period effect and did not persist over time. Conclusions In the intent-to-treat analysis, CSII appeared to be superior to MDI in reducing HbA1c and glucose AUC values without significant change in weight or insulin dose in obese, uncontrolled, insulin-treated Type 2 diabetic subjects. [source] Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizuresEPILEPSIA, Issue 9 2010Annelies Van Dycke Summary Purpose:, Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods:, Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 ,l/h) (treatment). In 7 of 10 adenosine-treated rats, saline was also delivered during a washout period. Results:, During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions:, This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures. [source] Pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western subjectsEPILEPSIA, Issue 8 2009Peter Zannikos Summary Purpose:, To compare the pharmacokinetics of carisbamate (RWJ-333369) in healthy Japanese and Western adults, and to comparatively assess carisbamate safety and tolerability between the two populations. Methods:, An open-label study was conducted in 24 Japanese and 24 Caucasian healthy subjects. Subjects received a single oral dose of 250 mg carisbamate on day 1 followed by a 3-day washout period; twice-daily dosing of 250 mg carisbamate on days 5,8; subsequently, 500 mg on days 9,12 and a single dose of 500 mg on day 13. Plasma samples were collected for a pharmacokinetic analysis on days 1, 8, and 13. Plasma and urine samples were analyzed for carisbamate and its urinary metabolites by liquid-chromatography-mass-spectrometry. Results:, Following a single dose, carisbamate Cmax and area under the curve (AUC) geometric mean ratios were 16.4% and 28.8% higher in Japanese than in Caucasians, respectively; these differences were statistically significant and their 90% confidence intervals (CIs) fell outside of the 80,125% limits, which are considered not to be of clinical significance. With dose,body weight normalization, Cmax and AUC were similar in Japanese and Caucasian subjects and the 90% CIs were within the 80,125% boundaries. Carisbamate was well tolerated, and its mean oral clearance and half-life were similar in both groups, ranging from 35.1,41.4 ml/h/kg and 11.5,12.8 h. Discussion:, Carisbamate plasma exposure (AUC) and Cmax in Japanese subjects is ,20,25% higher than in Caucasians due to a higher mg/kg dose. After body weight normalization, carisbamate pharmacokinetics was similar between Japanese and Caucasian subjects following single and multiple dosing, and showed the same dose proportionality. [source] Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2002G. Williams Abstract Background Patients with chronic fatigue syndrome (CFS) show evidence of circadian rhythm disturbances. We aimed to determine whether CFS symptoms were alleviated by melatonin and bright-light phototherapy, which have been shown to improve circadian rhythm disorders and fatigue in jet-lag and shift workers. Design Thirty patients with unexplained fatigue for > 6 months were initially assessed using placebo and then received melatonin (5 mg in the evening) and phototherapy (2500 Lux for 1 h in the morning), each for 12 weeks in random order separated by a washout period. Principal symptoms of CFS were measured by visual analogue scales, the Shortform (SF-36) Health Survey, Mental Fatigue Inventory and Hospital Anxiety and Depression Scale. We also determined the circadian rhythm of body temperature, timing of the onset of melatonin secretion, and the relationship between these. Results Neither intervention showed any significant effect on any of the principal symptoms or on general measures of physical or mental health. Compared with placebo, neither body temperature rhythm nor onset of melatonin secretion was significantly altered by either treatment, except for a slight advance of temperature phase (0·8 h; P = 0·04) with phototherapy. Conclusion Melatonin and bright-light phototherapy appear ineffective in CFS. Both treatments are being prescribed for CFS sufferers by medical and alternative practitioners. Their unregulated use should be prohibited unless, or until, clear benefits are convincingly demonstrated. [source] Constitutive opioid receptor activation: a prerequisite mechanism involved in acute opioid withdrawalADDICTION BIOLOGY, Issue 2 2005E Freye The opioid receptor antagonist naltrexone, which is used in detoxification and rehabilitation programmes in opioid addicts, can precipitate opioid withdrawal symptoms even in patients who have no opioid present. We tested the hypothesis that in order to precipitate withdrawal, opioids need to convert the inactive opioid receptor site via protein kinase C into a constitutively active form on which the antagonist precipitates withdrawal. Acute abstinence symptoms were induced by the potent opioid receptor agonist sufentanil (21?,g/kg), given for 6 days, which was followed by the antagonist naltrexone (20?,g/kg i.v.) in the awake trained canine (n,=,10). Abrupt displacement of opioid binding resulted in acute withdrawal symptoms: increase in blood pressure, heart rate, increase in amplitude height of somatosensory evoked potential, reduced tolerance to colon distention and a significant increase in grading of vegetative variables (restlessness, panting, thrashing of the head, whining, yawning, gnawing, salivation and/or rhinorrhoea, mydriasis, stepping of extremities and vomiting). Following a washout period of 14 days, the same animals were given the highly specific protein kinase C inhibitor H7 (250?,g/kg) prior to the same dosages of sufentanil and naltrexone. Such pretreatment was able to either attenuate or completely abolish the acute withdrawal symptoms. The data suggest that for precipitation of withdrawal, intracellular phosphorylation is a prerequisite in order to activate the opioid ,-receptor. In such a setting, naltrexone acts like an ,inverse agonist? relative to the action of the antagonist on a non-preoccupied receptor site not being exposed previously to a potent opioid agonist. [source] PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Joshua S. Rodefer Abstract Persistent suppression of N -methyl- d -aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions in a pattern similar to changes reported in schizophrenia. This similarity suggests that chronic NMDA receptor antagonism in animals may represent a useful model of neurobiological and related cognitive deficits in schizophrenia. Schizophrenia is associated with impairments in frontal lobe-dependent cognitive functions, including working memory and attentional shifting. Deficits in attention and executive function have not been well characterized in animal models of schizophrenia using chronic NMDA receptor antagonist administration. We investigated whether subchronic systemic administration of the NMDA receptor antagonist phencyclidine (PCP) to rats followed by a drug washout period would produce enduring cognitive deficits on an attentional set-shifting task. The task is functionally analogous to a sensitive test of frontal function in humans and non-human primates. Subchronic PCP administration selectively impaired extradimensional shift learning without affecting other discrimination or reversal tasks. Moreover, acute treatment with the PDE10A inhibitor papaverine immediately prior to testing attenuated the PCP-induced deficits in extradimensional shift learning across a range of doses. These data suggest that subchronic PCP administration may model effectively some of the cognitive deficits that are observed in schizophrenia, and that PDE10A inhibition may be an effective therapeutic route to improve executive function deficits associated with schizophrenia. [source] Comparison of Routes of Flumazenil Administration to Reverse Midazolam-induced Respiratory Depression in a Canine ModelACADEMIC EMERGENCY MEDICINE, Issue 5 2000Melanie S. Heniff MD ABSTRACT Objective: To determine whether flumazenil, a drug used to reverse benzodiazepine-induced respiratory depression and approved only for IV use, is effective by alternative routes. Methods: A randomized, controlled, nonblinded, crossover canine trial was performed to evaluate reversal of midazolam-induced respiratory depression by flumazenil when administered by alternative routes. Mongrel dogs were sedated with thiopental 19 mg/kg IV, then tracheally intubated. With the dogs spontaneously breathing, tidal volume, end-tidal CO2, and O2 saturation were observed until a stable baseline was achieved. Incremental doses of midazolam were administered until respiratory depression (30% decline in tidal volume, 10% decrease in O2 saturation, and 15% increase in end-tidal CO2) occurred. Flumazenil was administered by a randomly selected route [0.2 mg followed 1 minute later by 0.3 mg IV, sublingual (SL) or intramuscular (IM); or 1 mg followed 1 minute later by 1.5 mg per rectum (PR)]. Time to return to baseline respiratory functions was recorded ("time to reversal"). Each of 10 dogs was studied using all 4 routes of flumazenil administration with a washout period of at least 7 days. An additional dog served as a control (no flumazenil). Results: The control time to reversal was 1,620 seconds. The IV route was significantly faster (mean 120 ± 24.5 sec) than the other 3 routes (p < 0.005). The SL route was the second fastest (mean 262 ± 94.5 sec), the IM route was the third fastest (mean 310 ± 133.7 sec), and the PR route was the slowest (mean 342 ± 84.4 sec). The SL, IM, and PR routes did not differ significantly from one another. Conclusions: Flumazenil administered by all 4 routes reversed midazolam-induced respiratory depression in a dog model. For the selected dosages used, the IV route was significantly faster than all 3 other routes, and SL was the second fastest. [source] Conduction block and glial injury induced in developing central white matter by glycine, GABA, noradrenalin, or nicotine, studied in isolated neonatal rat optic nerveGLIA, Issue 11 2009Stavros Constantinou Abstract The damaging effects of excessive glutamate receptor activation have been highlighted recently during injury in developing central white matter. We have examined the effects of acute exposure to four other neurotransmitters that have known actions on white matter. Eighty minutes of Glycine or GABA-A receptor activation produced a significant fall in the compound action potential recorded from isolated post-natal day 10 rat optic nerve. This effect was largely reversed upon washout. Nicotinic acetylcholine receptor (nAChR) or adrenoreceptor activation with noradrenalin resulted in an ,35% block of the action potential that did not reverse during a 30-min washout period. While the effect of nAChR activation was blocked by a nAChR antagonist, the effect of noradrenalin was not ablated by ,- or ,-adrenoreceptor blockers applied alone or in combination. In the absence of noradrenalin, co-perfusion with ,- and ,-adrenoreceptor blockers resulted in nonreversible nerve failure indicating that tonic adrenoreceptor activation is required for nerve viability, while overactivation of these receptors is also damaging. Nerves exposed to nAChR + adrenoreceptor activation showed no axon pathology but had extensive glial injury revealed by ultrastructural analysis. Oligodendroglia exhibited regions of membrane vacuolization while profound changes were evident in astrocytes and included the presence of swollen and expanded mitochondria, vacuolization, cell processes disintegration, and membrane breakdown. Blinded assessment revealed higher levels of astrocyte injury than oligodendroglial injury. The findings show that overactivation of neurotransmitter receptors other than those for glutamate can produce extensive injury to developing white matter, a phenomenon that may be clinically significant. © 2009 Wiley-Liss, Inc. [source] Low-Dose Topiramate Versus Lamotrigine in Migraine Prophylaxis (The Lotolamp Study)HEADACHE, Issue 3 2007Praveen Gupta MD Objective.,To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo. Methods.,Sixty patients with frequent migraine (more than 4 attacks per month) from the headache clinic at a tertiary referral centre in India were randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between. Primary efficacy measure was responder rate (50% decrease in mean migraine frequency/intensity). Secondary efficacy measures included reduction in mean monthly frequency, intensity, duration, rescue medication use, migraine associated symptoms, and adverse events. Statistical analysis.,Analysis was on intention to treat basis. Data were analyzed as correlated data. Generalized estimation equation was used to compute overall mean standard deviation and 95% confidence intervals for each of the outcome variables. Bonferroni's correction done for multiple comparisons. P value of <.017 was taken as significant. Results.,Fifty-seven patients comprised the intent-to-treat population. Four patients withdrew from the study at various phases, none because of the side effects. Responder rate for frequency was significantly higher for topiramate versus placebo (63% vs 30%, P < .001), and versus lamotrigine (63% vs 46 %, P= .02). For intensity of headache also a responder rate of topiramate versus placebo (50% vs 10%, P < .001), and versus lamotrigine (50% vs 41%, P= .01) was observed. Topiramate showed statistically significant benefits (P < .017) in most of the secondary efficacy measures while lamotrigine was beneficial for reduction in headache frequency, and migraine associated symptoms. Adverse events were similar. Conclusion.,Low-dose topiramate is efficacious in migraine prophylaxis as compared to both placebo and lamotrigine. Lamotrigine in low doses might be beneficial for headache frequency; however, longer trials are required to establish its efficacy on the intensity and frequency of migraine. [source] Electroacupuncture for Tension-type Headache on Distal Acupoints Only: A Randomized, Controlled, Crossover TrialHEADACHE, Issue 4 2004C. C. L. Xue PhD Objective.,To investigate the efficacy of electroacupuncture, applied to distal acupoints only, for tension-type headache. Background.,Electroacupuncture is commonly used for tension-type headache, but when applied to distal acupoints only, evidence of its efficacy is lacking. Design.,A randomized, single-blinded, sham-controlled, crossover clinical trial. Methods.,The trial had 5 stages: baseline (2 weeks), phases I and II (each 4 weeks), washout period (2 weeks), and follow-up (3 months after phase II). Forty patients were randomly assigned to either group A or group B. Group A received real electroacupuncture during phase I, then sham electroacupuncture in phase II. Group B received the treatments in reverse order. Outcome measures were headache frequency and duration, pain intensity using a visual analog scale, mechanical pain threshold, headache disability, and sickness impact. Data were analyzed by univariate 2-way analysis of variance. Results.,Thirty-seven patients completed the trial. There were no significant differences between the 2 groups at baseline. At the end of phase I, group A, but not group B, demonstrated significant improvement in mean (standard error of the mean [SEM]) headache frequency (3.0 per month [0.3] versus 12.0 per month [1.7]), duration (13.3 hours [3.5] versus 32.0 hours [6.2]), pain intensity (32.8 mm [4.1] versus 47.5 mm [2.7]), pain threshold (right side, 2.9 kg/second [0.1] versus 0.9 kg/second [0.1]; left side, 2.4 kg/second [0.1] versus 1.1 kg/second [0.1]), headache disability score (6.0 [1.0] versus 16.3 [1.6]), and sickness impact score (288.7 [48.0] versus 687.1 [77.2]). For each parameter, significant differences also were demonstrated for both groups between baseline and phase II, and baseline and follow-up. There were no significant differences between the groups at the end of follow-up (P > .05). Conclusion.,Electroacupuncture to distal points alone is effective for short-term symptomatic relief of tension-type headache. [source] A placebo controlled investigation into the effects of paroxetine and mirtazapine on measures related to car driving performanceHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2003F. Ridout Abstract Objective To assess the effects of paroxetine and mirtazapine on psychometric performance related to car driving, including an on-the-road test of BRT. Method In a 4-way, double blind randomised crossover study, 12 healthy volunteers received paroxetine 20,mg mane, mirtazapine 15,mg/30,mg nocte (comparator), mirtazapine 15,mg mane/15,mg b.i.d.(verum) and placebo over a 5 day period with a washout period of 7 days between treatments. Psychometric assessments included ,on-the-road' BRT (BRT), CFF (CFF), CRT (CRT) and subjective measures of sedation and sleep parameters. Results Paroxetine had no significant effect on BRT compared with placebo. Although subjective ratings of sleep quality and sedation were impaired, there were significant improvements in both CFF and the recognition reaction component of CRT with paroxetine. Mirtazapine 15,mg/30,mg nocte impaired laboratory performance and some subjective tests. Mirtazapine 15 mg mane/15,mg b.i.d. improved sleep, but significantly impaired all other measures. Conclusion Paroxetine 20,mg/day has no psychomotor or behavioural toxicity and has no negative impact on BRT. Further research into the chronic and sub-chronic effects of mirtazapine is needed to establish the clinical significance of these results. Copyright © 2003 John Wiley & Sons, Ltd. [source] Effectiveness of kukui nut oil as a topical treatment for psoriasisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2005Amy C. Brown PhD Background, No cure for psoriasis exists for the 1,3% of the American population who suffer from it; however, anecdotal reports from patients with psoriasis visiting Hawaii who purchased kukui nut oil, claim it helped reduce the severity of their lesions. Objective, This pilot study was a double-blind, placebo-controlled clinical trial to determine the effectiveness of kukui nut oil as a topical treatment for psoriasis. Methods, Thirty adult subjects (18,78 year) were recruited from the community for a 12-week randomized, double-blind, placebo-controlled pilot study. Subjects were previously diagnosed with mild, stable plaque psoriasis (less than 15% of total body surface area [TBSA]) and agreed to abstain from other treatments during the course of the study. Following a 4-week washout period the subjects were randomized into a treatment group (15 subjects applying kukui nut oil) or a control group (15 applying the mineral oil placebo). Patients were seen every 2 weeks (seven visits at 0, 2, 4, 6, 8, 10, and 12 weeks) by a dermatological nurse practitioner under the general supervision of a board certified dermatologist. Measurable outcomes included evaluation of one targeted lesion and of the overall severity of their psoriasis using clinical evaluation, Psoriasis Area and Sensitivity Index (PASI), Global Severity of Psoriasis Scale, and photographs. Each patient also evaluated their own lesions daily using the Global Severity of Psoriasis Scale, and noted any side-effects or other treatments used. Results, Although both groups improved, we found no significant difference between the treatment (kukui nut oil) and the placebo (mineral oil) among the 24 out of 30 subjects (80%) who completed the study. No side-effects or adverse events were reported. Conclusion, Kukui nut oil did not significantly reduce symptoms of psoriasis; however, this was a small pilot study, and the use of this oil cannot be dismissed without using a larger study population of patients with psoriasis. [source] Influence of a SLS-containing dentifrice on the anti-plaque efficacy of a chlorhexidine mouthrinseJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2004D. A. C. Van Strydonck Abstract Background: Chlorhexidine (CHX) and sodium lauryl sulphate (SLS), the most widely used detergent in dentifrice, may counteract. Consequently, studies about this interaction suggested that care is required when combining both these compounds, even when they are introduced separately into the oral cavity. The purpose of the present study was to investigate the effect of toothbrushing with a SLS-containing dentifrice in one jaw, on the plaque inhibition of a CHX mouthrinse in the opposite jaw during a 4-day study period. Methods: The study was an examiner-blind, randomised two-cell, crossover design. It used a 4-day plaque accumulation model to compare two different oral hygiene regimens with a washout period of 17 days. Sixteen healthy volunteers were enrolled in the study and received a thorough dental prophylaxis at the beginning of each 4-day test period. One jaw (upper or lower) was randomly assigned as the "study" jaw. The opposite jaw was assigned as the "dentifrice" jaw and served only to introduce the effect of brushing with a dentifrice in the study model. Two oral hygiene regimens were evaluated. During one randomly assigned test period, the "dentifrice" jaw was treated by toothbrushing with a 1.5% SLS-containing dentifrice and rinsed together with the "study" jaw with 0.2% CHX, thus forming regimen 1. As a control during the other test period, both the "dentifrice" jaw and "study" jaw were only rinsed with 0.2% CHX, forming regimen 2. No other oral hygiene methods were allowed. After 4 days of undisturbed plaque accumulation, the amount of plaque was evaluated (Silness & Löe 1964). The "study" jaw was used to study the effect of the two regimens on the level of plaque accumulation at the end of the 4-day period. Results: The overall plaque index was 0.36 for regimen 1 and 0.34 for regimen 2. There was no significant difference in plaque accumulation between the two regimens. Conclusions: Within the limitations of the present study design, it can be concluded that ordinary brushing with a 1.5% SLS-containing dentifrice (Colgate Bi-Fluor), followed by rinsing with water does not appear to reduce the level of plaque inhibition offered by a post-brushing CHX rinse. [source] Effects of 0.2% chlorhexidine spray applied once or twice daily on plaque accumulation and gingival inflammation in a geriatric populationJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2003Javier Clavero Abstract Background/aims: Chlorhexidine (CHX) spray has proven to be an easily applicable method for the chemical control of plaque in elderly and handicapped patients. A randomized double-blind cross-over placebo-controlled trial was undertaken to compare the effects of 0.2% CHX spray applied once or twice daily on the plaque and gingival indexes in 13 institutionalized elderly patients. Method: The study subjects were randomly assigned to one of two groups. During the first 30-day period, one group received 0.2% chlorhexidine spray twice daily and the other received 0.2% CHX spray once daily plus placebo spray once daily. A washout period of 42 days then followed, after which the groups were interchanged and the process was repeated for another 30-day period. Plaque index and gingival index were determined at the beginning and end of each period. The patients continued with their usual oral hygiene practices throughout the study. Results: A significant reduction in plaque and gingival indexes was produced in both the groups. There were no significant differences in index scores between the groups. Conclusions: The results of the present study suggest that a single-daily application of 0.2% CHX spray is equally as effective in reducing plaque accumulation and gingival inflammation in institutionalized elderly patients as are two-daily applications of the same spray. Zusammenfassung Grundlagen/Ziele: Es hat sich herausgestellt, dass Chlorhexidinspray eine leicht zu handhabende Methode der chemischen Plaquekontrolle bei älteren und behinderten Patienten ist. Um die Unterschiede zwischen ein- oder zweimaliger Applikation von 0.2%-Chlorhexidinspray auf die Plaque- und Gingiva-Indizes zu vergleichen wurde an 13 institutionalisierten älteren Patienten eine randomisierte Plazebo-kontrolierte Crossover-Studie unternommen. Methode: Die Studienteilnehmer wurden randomisiert einer von zwei Gruppen zugeteilt. Während der ersten 30-Tageperiode erhielt eine Gruppe zweimal täglich 0.2%-Chlorhexidinspray und die andere Gruppe einmal täglich 0.2%-Chlorhexidinspray und einmal täglich einen Plazebo-Spray. Es folgte eine Auswaschperiode von 42 Tagen, nach der die Gruppen vertauscht wurden und der Prozess für weitere 30 tage wiederholt wurde. Zu Beginn und am ende einer jeden Periode wurden Plaque-Index (PI) und Gingival-Index (GI) bestimmt. Während der ganzen Studienperiode praktizierten die Patienten ihre üblichen Mundhygienemaßnahmen. Ergebnisse: In beiden Gruppen ergab sich eine signifikante Reduktion der Plaque- und Gingiva-Indizes. Zwischen den beiden Gruppen gab es keine signifikanten Unterschiede der Indexwerte. Schlussfolgerungen: Die Ergebnisse der vorliegenden Studie lassen annehmen, dass bei institutionalisierten älteren Patienten eine einzige Applikation pro Tag von 0.2%-Chlorhexidinspray bei der Reduktion der Plaqueakkumulation sowie der Gingivaentzündung genauso effektiv ist, wie die täglich zweimalige Applikation des gleichen Sprays. Résumé Le spray de chlorhexidine (CHX) a prouvé sa facilité d'application pour le contrôle chimique de la plaque dentaire chez les patients âgés et handicapés. Un essai clinique contrôlé, croisé, en double aveugle, randomisé et placebo-contrôle a été entrepris pour comparer les effets d'un spray de CHX 0.2% appliqué une ou deux fois par jour sur la plaque dentaire et les indices gingivaux de patients âgés de douze institutions. Les sujets ont été répartis en deux groupes. Durant une première période de 30 jours, un groupe recevait un spray de CHX 0.2% deux fois par jour tandis que l'autre recevait un spray de CHX 0.2% un fois par jour plus un spray placebo une fois par jour. Une période sans traitement de 42 jours a ensuite étéétablie suivie à la suite de laquelle les groupes ont été interchangés et le processus répété pour une nouvelle période de 30 jours. L'indice de plaque dentaire et l'indice gingival ont été déterminés au début et à la fin de chaque période. Les patients ont continué leurs habitudes d'hygiène buccale habituelles durant toute l'étude. Une réduction significative des indices de plaque et de gencive ont été relevés dans les deux groupes. Il n'y avait aucune différence significative de scores entre les deux groupes. Les résultats de l'étude présente suggèrent qu'une application unique d'un spray de CHX 0.2% est tout aussi efficace dans la réduction de la plaque dentaire et l'inflammation gingivale chez les patients âgés qu'une double application du même spray. [source] Effect of an essential oilcontaining antiseptic mouthrinse on plaque and salivary Streptococcus mutans levelsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2000D. H. Fine Abstract Background: Clinical studies in which antimicrobial mouthrinses were shown to have significant antiplaque activity most frequently have used gingivitis as the clinically relevant endpoint. However, there is evidence to suggest that mouthrinses containing active agents effective against Streptococcus mutans, such as chlorhexidine, may also have a rôle in inhibiting dental caries. This clinical study was conducted to determine the effect of 2×-daily rinsing with an essential oilcontaining antiseptic mouthrinse (Listerine® Antiseptic) on levels of recoverable S. mutans and total streptococci in supragingival interproximal plaque and in saliva. Additionally, a follow-up in vitro study is reported which determined whether a differential susceptibility to the antiseptic mouthrinse exists among different strains of streptococci. Method: Following baseline saliva and plaque sampling for quantification of recoverable S. mutans and total streptococci, 29 qualifying subjects were randomly assigned either the essential oil mouthrinse or a sterile water control. They rinsed with 20 ml for 30 s 2×daily for 11 days and once on the 12th day, in addition to their usual oral hygiene procedures. On day 12, saliva and plaque samples were again collected and microbiological quantification performed. The procedures were repeated with the alternate rinse after a 1-week washout period. Results: The essential oil mouthrinse produced respective reductions of 69.9% and 75.4% in total recoverable streptococci and in S. mutans in plaque, and corresponding reductions of 50.8% and 39.2% in saliva. The in vitro study revealed that streptococci from the mutans group were more susceptible to the bactericidal activity of the essential oil mouthrinse than streptococci from the mitis group. Conclusions: As antimicrobial mouthrinses are most frequently recommended to patients whose mechanical oral hygiene procedures are not adequate for the control of supragingival plaque and gingivitis, this study provides an additional rationale for the inclusion of the essential-oil mouthrinse as an adjunct to daily oral hygiene procedures. [source] Reduced oral itraconazole bioavailability by antacid suspensionJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005M. Lohitnavy Summary Aims:, To investigate the effects of antacid suspension on oral absorption of itraconazole. Methods:, A randomized, open-labelled, two-period, crossover study with a 1-week washout period was conducted in 12 healthy Thai male volunteers. The participants were allocated in either treatment A or B in the first period. In treatment A, the volunteers were orally administered with 200 mg of itraconazole alone. In treatment B, the volunteers were administered orally with 200 mg of itraconazole co-administered with antacid suspension. Serial serum samples were collected over the period of 24 h and subsequently analysed by using a validated high-pressure liquid chromatographic method with ultraviolet detection. Pharmacokinetic parameters were determined by non-compartmental analysis. Results:, Time to reach maximal concentration (Tmax), maximal concentration (Cmax) and area under the curve (AUC0--,) were markedly decreased in antacid-treated group. Tmax for treatment A was 3·0 ± 0·4 and 5·1 ± 2·7 h for treatment B. Cmax and AUC0--, of treatments A and B were 146·3 ± 70·5 vs. 43·6 ± 16·9 (ng/mL) and 1928·5 ± 1114·6 vs. 654·8 ± 452·2 (ng·h/mL) respectively. 90% Confidence interval (90% CI) of Cmax and AUC0--, were 24·1,42·1 and 16·2,65·9 respectively. Conclusions:, Rate and extent of itraconazole oral absorption were markedly decreased by concurrent use of antacid suspension. Hence, co-administration of itraconazole and antacid suspension should be avoided. [source] Alpha lipoic acid in burning mouth syndrome , a randomized double-blind placebo-controlled trialJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2009Desirée Rosa Cavalcanti The burning mouth syndrome (BMS) is a chronic condition characterized by oral burning pain in the absence of clinical abnormalities and without established therapy. Objectives:, The purpose of this study was to evaluate the effectiveness of alpha lipoic acid (ALA) in the management of BMS symptoms through a randomized double-blind placebo-controlled trial. Methods:, Thirty-eight patients (34 women and four men, median age 62.9 years, range 36,78) were included and 31 completed the study. The patients were randomized into two cycles of treatment: one with alpha lipoic acid and one with placebo both administered in identical capsules. These cycles were separated by a washout period of 20 days. The oral symptoms and the treatment response were assessed using a 100-mm visual analog scale before and after each cycle and the global perceived effect score, using a 5-point scale after each treatment cycle. Results:, The level of reduction on burning was significant for both treatments (paired t -test: P < 0.05; rp = 0.011; ral < 0.001). Considering the two cycles together, 22 patients reported at least some improvement after ALA use and 23 patients after placebo. Conclusions:, Comparison of the oral assessment scores of the two cycles failed to demonstrate the effectiveness of ALA over placebo (t -test: P > 0.05; r = 0.75). [source] The effect of oral splint devices on sleep bruxism: a 6-week observation with an ambulatory electromyographic recording deviceJOURNAL OF ORAL REHABILITATION, Issue 7 2006T. HARADA summary, This study investigated the effect of stabilization splint (SS) and palatal splint (PS), which had the same design as SS except for the elimination of the occlusal coverage, on sleep bruxism (SB) using a portable electromyographic (EMG) recording system. Sixteen bruxers participated in this study. The EMG activities of the right masseter muscle during sleep were recorded for three nights each in the following five recording periods: before, immediately after, and 2, 4 and 6 weeks after the insertion of the splint. The crossover design, in which each splint was applied to each subject for 6 weeks with an interval of 2 months for a washout period, was employed in this randomized-controlled study. The number of SB events, duration and total activities of SB were analysed. The number of SB events before the insertion of splints (baseline) was 2·98 ± 1·61 times h,1. Both splints significantly reduced SB immediately after the insertion of devices (P < 0·05, one-way repeated-measures anova followed by Dunnett); however, no reduction was observed in 2, 4 or 6 weeks (P > 0·05). There was no statistical difference in the effect on SB between the SS and PS (P > 0·05, two-way repeated-measures anova). Both splints reduced the masseter EMG activities associated with SB; however, the effect was transient. [source] Proteomic Analysis Demonstrates Adolescent Vulnerability to Lasting Hippocampal Changes Following Chronic Alcohol ConsumptionALCOHOLISM, Issue 1 2009Garth A. Hargreaves Background:, Excessive teenage alcohol consumption is of great concern because alcohol may adversely alter the developmental trajectory of the brain. The aim of the present study was to assess whether chronic intermittent alcohol intake during the adolescent period alters hippocampal protein expression to a greater extent than during adulthood. Methods:, Adolescent [postnatal day (PND) 27] and adult (PND 55) male Wistar rats were given 8 hours daily access to beer (4.44% ethanol v/v) in addition to ad libitum food and water for 4 weeks. From a large subject pool, subgroups of adolescent and adult rats were selected that displayed equivalent alcohol intake (average of 6.1 g/kg/day ethanol). The 4 weeks of alcohol access were followed by a 2-week alcohol-free washout period after which the hippocampus was analyzed using 2-DE proteomics. Results:, Beer consumption by the adult group resulted in modest hippocampal changes relative to alcohol naïve adult controls. The only changes observed were an up-regulation of citrate synthase (a precursor to the Krebs cycle) and fatty acid binding protein (which facilitates fatty acid metabolism). In contrast, adolescent rats consuming alcohol showed more widespread hippocampal changes relative to adolescent controls. These included an increase in cytoskeletal protein T-complex protein 1 subunit epsilon (TCP-1) and a decrease in the expression of 10 other proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triose phosphate isomerise, alpha-enolase, and phosphoglycerate kinase 1 (all involved in glycolysis); glutamate dehydrogenase 1 (an important regulator of glutamate); methylmalonate-semialdehyde dehydrogenase (involved in aldehyde detoxification); ubiquitin carboxyl-terminal hydrolase isozyme L1 (a regulator of protein degradation); and synapsin 2 (involved in synaptogenesis and neurotransmitter release). Conclusions:, These results suggest the adolescent hippocampus is more vulnerable to lasting proteomic changes following repeated alcohol exposure. The proteins most affected include those related to glycolysis, glutamate metabolism, neurodegeneration, synaptic function, and cytoskeletal structure. [source] Opposing Effects of Chronic Alcohol Consumption on Hepatic Gluconeogenesis for Female Versus Male RatsALCOHOLISM, Issue 10 2005Ken D. Sumida Abstract: Background: The impact of chronic alcohol consumption on hepatic gluconeogenesis (HGN) between males and females is unknown. To determine the effects of chronic alcohol consumption (8 weeks) on HGN, the isolated liver perfusion technique was used on 24-hr-fasted male and female Wistar rats. Methods: After surgical isolation, livers were perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes with no added substrate (washout period). After the washout period, livers were perfused with lactate (10 mM) and [U- 14C]lactate (15,000 dpm/ml) using the recirculation method. Results: There was no significant difference in HGN between males and females fed the control diet. In contrast, the females chronically fed the ethanol diet (FE) had significantly lower HGN rates (2.73 ± 0.37 ,mol/min × g liver protein,1), whereas males fed the ethanol diet (ME) had significantly higher HGN rates (4.99 ± 0.45 ,mol/min × g liver protein,1) than controls (3.83 ± 0.34 ,mol/min × g liver protein,1). Concomitant decreases were also observed for both 14C-lactate incorporation into 14C-glucose and rates of lactate uptake for FE, while corresponding increases were observed for 14C-lactate incorporation into 14C-glucose for ME. The livers from ME were able to convert a greater percentage of the lactate into glucose, resulting in the elevation in gluconeogenic capacity. Conclusion: Chronic alcohol consumption lowers the hepatic gluconeogenic capacity from lactate in females and elevates HGN in males. [source] ANTICOAGULANT EFFECTS OF LOW MOLECULAR WEIGHT HEPARIN IN HEALTHY CATSJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue S1 2004AJ Alwood Objectives: 1) Validate a chromogenic assay to measure Factor Xa inhibitory activity (anti-Xa activity) in normal feline plasma and following administration of low molecular weight heparins and unfractionated heparin. 2) Compare the effects of two commercially available low molecular weight heparins (LMWH), unfractionated heparin (UFH), and placebo on TEG, anti-Xa activity, PT/aPTT, PCV/TS and platelet count in healthy cats. Methods: Our study consisted of two phases: 1) the evaluation of a commercially available chromogenic anti-Xa assay (Rotachrom Heparin, Diagnostic Stago) for use in cats, and 2) the evaluation of hemostatic effects of LMWH in healthy cats. Phase 1: The anti-Xa assay was validated for use in cats using feline plasma and serial dilutions of the plasma spiked with UFH, enoxaparin, and dalteparin. Phase 2: Five healthy cats were included in a randomized Latin Squares model crossover-design to compare the effects of UFH and LMWH in cats. The cats then received one of the following subcutaneously: 1) 250 IU/kg UFH QID, 2) 100 IU/kg dalteparin BID, 3) 1 mg/kg enoxaparin BID, 4) 0.25 mL/kg 0.9% saline (placebo) QID. A minimum of a two-week washout period separated each treatment period. Each drug was administered for 5 days. Blood samples were obtained to measure anti-Xa, TEG, PT/aPTT, platelet count, and PCV/TS on Days 1, 3, 5, and 6 of each treatment cycle. Samples were collected at time 0 on each sample day for all parameters and on select days at hours 4, 8, and 12 for anti-Xa and TEG. Results: Preliminary results using the validated anti-Xa assay (from the first part of this study) demonstrate that LMWH treatment results in peak anti-Xa activity at the 4-hour sampling time that returned toward baseline by 8 hours (in 5/6 cats treated with LMWH thus far). Similar anticoagulant effects were noted in the TEG parameters of cats receiving LMWH (i.e., peak effects were noted at 4 hours). Analysis of current data by linear regression identifies a relationship between anti-Xa measurements and TEG parameters for cats treated with all heparin therapies (p<0.001). A similar relationship exists between anti-Xa and aPTT. Conclusions: Preliminary results suggest an anticoagulant effect of LMWH in cats that may not be uniform across individuals. Anti-Xa activity or TEG may provide useful tools for monitoring LMWH. [source] Neurohormonal and Circulatory Effects of Short-Term Treatment with Enalapril and Quinapril in Dogs with Asymptomatic Mitral RegurgitationJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2005Sophia Gry Moesgaard The aim of the study was to compare the effect of 2 angiotensin-converting enzyme (ACE) inhibitors on neurohormonal and circulatory variables in Cavalier King Charles Spaniels (CKCSs) with asymptomatic mitral regurgitation (MR). Ten CKCSs with mild to severe untreated MR were treated with 2 ACE inhibitors, quinapril and enalapril (each at 0.5 mg/kg PO q24h for 7 days), in a double-blind, crossover study with a washout period of 7 days between treatments. Blood samples were drawn and echocardiography was performed on days 0, 7, 14, and 21. Both treatments reduced ACE activity (P < .001) and increased renin activity (P < .001) and atrial natriuretic peptide concentration (P < .005). The ACE inhibitors had no effect on the concentrations of nitrate and nitrite (NOx) or asymmetric dimethylarginine (ADMA). On day 0, a lower NOx concentration (P= .02) was found in samples taken in the clinic as compared to samples taken in the homes of the dogs. Quinapril caused a significant reduction in more variables that reflect the severity of MR (eg, jet size and left ventricular end diastolic diameter) than did enalapril. However, in terms of specific variables, no significant difference was identified between the effects of the 2 treatments on MR. These results suggest that ACE inhibitors do not affect NOx and ADMA concentrations in asymptomatic dogs, but exercise, stress, or some combination may influence NOx concentrations in these dogs. [source] The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan® at clinical and supraclinical dosesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2008T. WHITTEM This study aimed to determine the pharmacokinetic parameters and pharmacodynamics of alfaxalone in a 2-hydroxypropyl-,-cyclodextrin alfaxalone formulation (Alfaxan®, Jurox Pty Ltd, Rutherford, NSW, Australia) in cats after single administration at clinical and supraclinical dose rates and as multiple maintenance doses. First, a prospective two-period cross-over study was conducted at single clinical and supraclinical doses. Second, a single group multiple dose study evaluated the effect of maintenance doses. Eight (five female and three male) domestic cats completed the cross-over experiment and six female cats completed the multiple dose study. In the first experiment, alfaxalone was administered intravenously (IV) at 5 or 25 mg/kg with a washout period of 14 days. In the second experiment, alfaxalone was administered IV at 5 mg/kg followed by four doses each of 2 mg/kg, administered at onset of responsiveness to a noxious stimulus. Blood was collected at prescribed intervals and analysed by LCMS for plasma alfaxalone concentration. Noncompartmental pharmacokinetics were used to analyse the plasma alfaxalone data. The plasma clearance of alfaxalone at 5 and 25 mg/kg differed statistically at 25.1 and 14.8 mL/kg/min respectively. The elimination half lives were 45.2 and 76.6 min respectively. Alfaxalone has nonlinear pharmacokinetics in the cat. Nevertheless, for cats dosed with sequential maintenance doses, a regression line through their peak plasma concentrations indicated that there was no clinically relevant pharmacokinetic accumulation. The duration of nonresponsiveness after each maintenance dose was similar at approximately 6 min, indicating a lack of accumulation of pharmacodynamic effect. The cardiovascular and respiratory parameters measured in cats after administration of the labelled doses of Alfaxan® were stable. In conclusion, the pharmacokinetics of alfaxalone in cats are nonlinear. At clinical dose rates, however, neither alfaxalone nor its effects accumulated to a clinically relevant extent. Further, in the un-premedicated cat the induction and maintenance of surgical anaesthesia was free of untoward events after a dose of 5 mg alfaxalone/kg body weight followed by four sequential doses of 2 mg/kg as needed (i.e., approximately 7 to 8 mg/kg/h). [source] Pharmacokinetics and bioavailability of imidocarb dipropionate in swineJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2007D. SU A two-way crossover study was performed in eight healthy young pigs to determine the pharmacokinetics of imidocarb dipropionate (IMDP) following intravenous (2 mg/kg b.w.) and intramuscular (2 mg/kg b.w.) administrations. Each animal received one intravenous and one intramuscular injection with a 30-day washout period between the two-treatments. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) assay with UV detector at regular intervals for up to 24 h post-injection. Intravenous plasma concentration profiles best fit a three-compartmental model yielding a mean system clearance (Cl(s)) of 558 mL/kg·h and a mean half-life of 13.91 h. Mean imidocarb AUC(0,,) (,g·h/mL), Vc (L/kg), Vd(area)(L/kg) and MRT(0-t) (h) values were 3.58, 0.11, 14.36 and 1.46, respectively. Compartmental modeling of imidocarb, after intramuscular administration produced best fit for two-compartmental model yielding mean K, (h,1), Cmax (,g/mL), tmax (h), and bioavailability (%) of 3.89, 2.02, 0.54, and 86.57 for the 2 mg/kg dose level. The present studies showed that IMDP was rapidly absorbed, widely distributed, and slowly eliminated. No adverse effects were observed in any of the pigs after i.v. and i.m. administrations of IMDP. The favorable PK behavior, such as the long half-life, acceptable bioavailability indicated that it is likely to be effective in pigs. [source] Pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole in alpacasJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002J. Chakwenya The pharmacokinetics and bioavailability of trimethoprim-sulfamethoxazole (TMP-SMX) were studied in six healthy male-castrate alpacas (Lama pacos) after intravenous (i.v.) or oral (p.o.) drug administration of 15 mg/kg TMP-SMX using a crossover design with a 2-week washout period. After 90 days one group (n = 3) was given a p.o. dose of 30 mg/kg TMP-SMX and the other group (n = 3) was given a p.o. dose of 60 mg/kg TMP-SMX. After i.v. administration of 15 mg/kg of TMP-SMX the mean initial plasma concentration (C0) was 10.75 ± 2.12 ,g/mL for trimethoprim (TMP) and 158.3 ± 189.3 ,g/mL for sulfamethoxazole (SMX). Elimination half-lives were 0.74 ± 0.1 h for TMP and 2.2 ± 0.6 h for SMX. The mean residence times were 1.45 ± 0.72 h for TMP and 2.8 ± 0.6 h for SMX. The areas under the respective concentration vs. time curves (AUC) were 2.49 ± 1.62 ,g h/mL for TMP and 124 ± 60 ,g h/mL for SMX. Total clearance (Clt) for TMP was 21.63 ± 9.85 and 1.90 ± 0.77 mL/min kg for SMX. The volume of distribution at steady state was 2.32 ± 1.15 L/kg for TMP and 0.35 ± 0.09 L/kg for SMX. After intragastric administration of 15, 30 and 60 mg/kg the peak concentration (Cmax) of SMX were 1.9 ± 0.8, 2.6 ± 0.4 and 2.8 ± 0.7 ,g/mL, respectively. The AUC was 9.1 ± 5, 25.9 ± 3.3 and 39.1 ± 4.1 ,g h/mL, respectively. Based upon these AUC values and correcting for dose, the respective bioavailabilities were 7.7, 10.5 and 7.94%. Trimethoprim was not detected in plasma after intragastric administration. These data demonstrate that therapeutic concentrations of TMP-SMX are not achieved after p.o. administration to alpacas. [source] Plasma pharmacokinetics of warfarin enantiomers in catsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2000S.A. SMITH The purpose of this study was to determine the dispositions of S-warfarin and R-warfarin in normal cats following intravenous and oral administrations of racemic warfarin. Citrated blood samples were collected from 10 cats prior to and at times 5, 15, and 30 min, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 72, 96, and 120 h following a single intravenous bolus of 0.5 mg/kg of racemic warfarin. After a 21-day washout period, samples were then similarly collected in three groups of four cats for 120 h following oral administration of 0.1, 0.25, and 0.5 mg/kg racemic warfarin. S-warfarin and R-warfarin were detected using a high-performance liquid chromatography assay validated for cat plasma. Drug concentration,time curves were subjected to non-compartmental analysis. Median pharmacokinetic parameters associated with the intravenous administration of 0.5 mg/kg racemic warfarin were as follows: t1/2 (S:28.2, R:18.3 h), area under the plasma concentration,time curve (AUC; S:33.0, R:24.6 h*,g/mL), area under the moment curve (AUMC; S:1889, R:527.8 h*h*,g/mL), and mean residence time (MRT; S:38.7, R:20.9 h). For each parameter, S-warfarin was significantly different from R-warfarin (P<0.05). Warfarin was absorbed rapidly after oral administration, and the dosage did not affect the time to maximum concentration (S:0.87, R:0.75 h). Oral dosage significantly influenced maximum plasma concentration (ng/mL, S:1267, R:1355 at 0.5 mg/kg; S:614.9, R:679.4 at 0.25 mg/kg; S:250.5, R:367.6 at 0.1 mg/kg), AUC (h*,g/mL, S:45.12, R:30.91 at 0.5 mg/kg; S:22.98:, R:18.99 at 0.25 mg/kg; S:3.922, R:3.570 at 0.1 mg/kg) and AUMC (h*h*,g/mL, S:2135, R:1062 at 0.5 mg/kg; S:943.1, R:599.9 at 0.25 mg/kg; S:132.2, R:59.03 at 0.1 mg/kg), but not t1/2 (S:23.5, R:11.6 h) nor MRT (S:26.3, R:13.5 h). Both warfarin enantiomers were highly (>96.5%) protein-bound. Quantitation of the warfarin content in commercially available tablets indicated an unequal distribution of the drug throughout the tablet. [source] Comparison of plasma pharmacokinetics and bioequivalence of ceftiofur sodium in cattle after a single intramuscular or subcutaneous injectionJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2000S. A. Brown Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. This study was designed to compare the bioequivalence of the sodium salt in cattle after a single intramuscular (i.m.) or subcutaneous dose (s.c.) of 2.2 mg ceftiofur equivalents/kg body weight. The criteria used to evaluate bioequivalence were (1) the area under the curve from time of injection to the limit of quantitation (LOQ) of the assay (AUC0-LOQ), and (2) time concentrations remained above 0.2 ,g/mL (t>0.2). Twelve crossbred beef cattle were enrolled in a three-period, two-treatment crossover trial, with a minimum 2-week washout period between doses of 2.2 mg ceftiofur equivalents/kg. Blood samples were collected serially for up to 72 h post-injection. Plasma samples were then analyzed using a validated assay that measures ceftiofur, and all desfuroylceftiofur-related metabolites, by high-performance liquid chromatography (HPLC) as the stable derivative, desfuroylceftiofur acetamide. A maximum plasma concentration (Cmax) of 13.9±3.55 ,g/mL was observed from 0.67,2.0 h after i.m. administration, whereas a Cmax of 13.6±3.85 ,g/mL was observed from 0.67,3.0 h after s.c. administration. The AUC0-LOQ was 108±35.0 ,g · h/mL after i.m. dosing, compared with 105±29.8 ,g · h/mL after s.c. dosing. The pre-established criterion for equivalence of the AUC0-LOQ for the i.m. and s.c. routes of administration was satisfied. The t>0.2 was 49.2±8.55 h after i.m. administration, compared with 47.0±9.40 h after s.c. administration. The pre-established criterion for equivalence of the t>0.2 for i.m. and s.c. administration was satisfied. The equivalence of AUC0-LOQ and t>0.2 for i.m. and s.c. administration of 2.2 mg ceftiofur equivalents (CE)/kg doses of ceftiofur sodium suggest similar therapeutic efficacy and systemic safety for the two routes of administration. [source] The pharmacokinetics and effects of intravenously administered carprofen and salicylate on gastrointestinal mucosa and selected biochemical measurements in healthy catsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2000Parton The pharmacokinetics of carprofen, a propionic acid-derived nonsteroidal anti-inflammatory (NSAID), and its effect on gastrointestinal mucosa, complete blood counts (CBC) and biochemical indicators of liver and renal function were investigated in healthy cats using a randomized crossover design. A single dose of 4 mg/kg of carprofen (Zenecarp® Injection), normal saline, or 20 mg/kg of DL-lysine acetyl salicylate (Vetalgine®) was given intravenously (i.v.) to each of five cats with a washout period of 2 weeks between treatments. Endoscopy of the stomach and duodenum 8 h postinjection revealed one acetyl salicylate-(aspirin)-treated cat with minor pinpoint erosions. None of the other cats in the three treatment groups had evidence of bleeding or ulceration. Serum biochemistry measurements of blood urea nitrogen (BUN), alanine transferase (ALT) and alkaline phosphatase (ALP) and complete blood counts (CBC) were not significantly altered from pretreatment values by the single dose of salicylate or carprofen (P < 0.05). Early and extended sample time points suggest that the pharmacokinetics of carprofen in the cat fit a 2-compartment model, with a long elimination half-life (t1/2) of 20.1 ± 16.6 h, an area under the plasma concentration,time curve (AUC) of 637 (± 237) ,g.mL/h and a volume of distribution (Vdss) of 0.14 ± 0.05 L/kg. Intravenously administered aspirin fit a 2-compartment model and had a long elimination half-life (t1/2) of 22.2 ± 3.1 h, an AUC of 3824.2 ± 506.7 ,g.mL/h and a volume of distribution (Vdss) of 0.17 ± 0.01 L/kg. [source] Oral rabeprazole vs. intravenous pantoprazole: a comparison of the effect on intragastric pH in healthy subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2007D. ARMSTRONG Summary Background Intravenous pantoprazole is often administered inappropriately to hospitalized patients who can take oral medications. Aim To compare the antisecretory effects of oral rabeprazole and intravenous pantoprazole in healthy subjects. Methods In a double-blind, double-dummy, two-way crossover study, 38 Helicobacter pylori -negative volunteers were randomized to oral rabeprazole 20 mg or intravenous pantoprazole 40 mg daily for 3 days followed, after a 14-day washout period by the comparator treatment. Intragastric pH was recorded continuously for 24 h at baseline and on days 1 and 3 of each treatment period. Results The mean (95% CI) percentage of the 24-h recording with gastric pH >4 was higher with rabeprazole than with pantoprazole on day 1: 37.7% (30.6,44.8%) vs. 23.9% (20.0,27.8). The mean percentage times with pH >3 and >4 for all intervals assessed were greater and the median 24-h intragastric pH values were higher with rabeprazole than with pantoprazole on days 1 and 3. The mean acidity index was lower with rabeprazole on days 1 and 3. Conclusions Oral rabeprazole 20 mg produced greater acid suppression than intravenous pantoprazole 40 mg. Therefore, it may be an appropriate and effective alternative in patients who can take oral medication. [source] | |||||||||||||||||||||||||||||||