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Selected AbstractsCLINICAL AND IMAGING STUDY: Glucocorticoid negative feedback in methadone-maintained former heroin addicts with ongoing cocaine dependence: dose,response to dexamethasone suppressionADDICTION BIOLOGY, Issue 1 2006Bruno Aouizerate ABSTRACT Combined cocaine and illicit opiate use is common. This study aimed to test the hypothesis that cocaine dependence in former heroin-addicted patients maintained on methadone treatment is associated with enhanced glucocorticoid negative feedback. Multiple dose dexamethasone suppression tests, using a conventional 2.0 mg dose, and two lower doses, 0.5 mg and 0.125 mg, were performed in 10 methadone-maintained former heroin addicts with ongoing cocaine dependence (C-MM), 10 stabilized methadone-maintained former heroin addicts with no ongoing drug or alcohol use (MM), and 22 normal volunteers (NV). At 9 hours, there was no difference in plasma adrenocorticotropin hormone (ACTH) and/or cortisol levels among groups on the baseline day, as well as after the two lower doses of dexamethasone. At 17 hours, C-MM and MM had significantly lower plasma ACTH and/or cortisol levels than NV. However, C-MM did not significantly differ from MM in their hormonal levels. When the hormonal responses to dexamethasone are expressed as magnitude of lowering from baseline, there was no significant difference at any dose among groups. Therefore, C-MM exhibited a normal glucocorticoid negative feedback in the morning. Using the standard interpretation of dexamethasone suppression testing based on the examination of the actual hormonal levels rather than the difference from baseline condition, C-MM appear to have glucocorticoid effects similar to MM, yet were both greater than NV in the late afternoon. Thus, further studies are needed to know whether altered glucocorticoid negative feedback is related to chronic cocaine exposure, or is the result of former heroin addiction and/or its long-term treatment with methadone. [source] The 40-mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mgEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2004Hans-Christoph Diener Meta-analysis provides valuable information regarding relative efficacies of triptans, but head-to-head comparator studies remain the gold standard. Three similar head-to-head trials comparing eletriptan 40 mg (E40) with sumatriptan 100 mg (S100) provide a rare opportunity and sufficient power, for robust comparisons of efficacy. Data were combined from three double-blind, placebo-controlled, first-dose, first-attack acute migraine treatment studies comparing E40 (n = 1132), S100 (n = 1129), and placebo (n = 645). The primary outcome was headache response at 2 h. Secondary outcomes included headache response at 1 h, pain-free and functional responses, and sustained headache and pain-free responses. Odds ratios were calculated for summary estimates of probability of response. There were higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs. 57%; P < 0.0001) and 1 h (34% vs. 26%; P < 0.0001). Eletriptan also had higher 2 h pain-free (35% vs. 25%; P < 0.0001) and functional responses (67% vs. 58%; P < 0.0001). Sustained headache (42%) and pain-free (22%) response rates were higher for eletriptan versus sumatriptan (34%, P < 0.0001; 15%, P < 0.0001). The probability of response for eletriptan versus sumatriptan ranged from 36% higher (relief of nausea) to 64% higher (sustained pain-free rate). Combined analysis demonstrates that E40 has superior efficacy versus S100 across all clinically relevant outcomes. [source] Subcutaneous Sumatriptan Pharmacokinetics: Delimiting the Monoamine Oxidase Inhibitor EffectHEADACHE, Issue 2 2010Anthony W. Fox (Headache 2010;50:249-255) Background., The absolute bioavailability of subcutaneous (s.c.) sumatriptan is 96-100%. The decay curve for plasma concentration after 6 mg s.c. sumatriptan (ie, after Tmax = about 0.2 hours) includes a large distribution component. Metabolism by monoamine oxidase-A (MAO-A) leads to about 40% of the s.c. dose appearing in the urine as the inactive indole acetic acid. Product labeling states that co-administration of an inhibitor of MAO-A (a MAOI-A) causes a 2-fold increase in sumatriptan plasma concentrations, and a 40% increase in elimination half-life. Objective., The objective of this study is to determine whether MAOI-A therapy should deter the use of 6 mg s.c. sumatriptan on pharmacokinetic grounds. Methods., Summary pharmacokinetic data were taken from the literature and from GlaxoSmithKline (GSK) study C92-050. Half-times were converted into rate constants, which were then used in a parsimonious compartmental model (needing only 3 simultaneous differential equations). Acceptance criteria for the model included observed plasma sumatriptan concentrations at Tmax, 1, 2, and 10 hours post-dose. A set of 1000 concentration measurements at a resolution of 36 seconds was generated. The model was then perturbed with elimination constants observed during concomitant moclobemide administration, creating a second set of concentration measurements. The 2 sets were then plotted, examined for their differences, and integrated for a second time to obtain and compare areas under the curve (AUCs). Results., The greatest absolute difference between the 2 sets of measurements was 2.85 ng/mL at t = 2.95 hours. A 2-fold difference between the 2 sets occurred only after t = 5.96 hours, when the concentration in the presence of the MAOI-A was 3.72 ng/mL (or <4% of Cmax). At t = 10 hours, the concentrations in both sets were <1 ng/mL (ie, below the lower limit of assay quantitation), and AUC0-10h was 97.4 and 117 ng.hour/mL in the absence and presence of the MAOI-A. Conclusions., There are no pharmacokinetic grounds to deter co-administration of an MAOI-A and subcutaneous sumatriptan. The dominance of the distribution phase and completeness of absorption of a 6 mg dose of s.c. sumatriptan explains the trivial effect size of the MAOI-A on plasma sumatriptan concentrations. Importantly, these findings should not be extrapolated to other routes of administration for sumatriptan. [source] Long-Term Tolerability of Sumatriptan Nasal Spray in Adolescent Patients With MigraineHEADACHE, Issue 10 2004Shankar Natarajan MD Objective.,This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. Methods.,A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. Results.,A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n = 4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). Conclusion.,Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years. [source] Almotriptan Reduces the Incidence of Migraine-Associated Symptoms: A Pooled AnalysisHEADACHE, Issue 2002Roger Cady MD Objectives.,Evaluate the reduction in migraine-associated symptoms after administration of a single oral dose of almotriptan. Methods.,This pooled analysis (N=1773) used data from three randomized, placebo-controlled, phase III trials (studies A, B, and C) to determine the incidence of migraine-associated symptoms (defined as nausea, vomiting, photophobia, and phonophobia) 2 hours after a single oral dose of study medication (almotriptan, sumatriptan, or placebo). Outcome data was extracted from studies A and B for placebo and the almotriptan 6.25-mg and 12.5-mg groups, and from study C for placebo, almotriptan 12.5-mg, and sumatriptan 100-mg groups. Results.,The incidence of nausea, photophobia, and phonophobia at 2 hours after dosing with study medication was significantly reduced (all P < .05) with almotriptan 6.25 mg or 12.5 mg compared with placebo. The percentage of patients with vomiting was lower with both doses of almotriptan in studies A and B compared with placebo, although differences were significant only for the 6.25-mg dose in study A (P < .001). For study C, the incidence of nausea, vomiting, photophobia, and phonophobia was similar for almotriptan and sumatriptan and lower than with placebo at 2 hours after dosing. Significant reductions (all P < .05) versus placebo were observed in the incidence of vomiting and phonophobia with almotriptan 12.5 mg, and photophobia and phonophobia with sumatriptan 100 mg. Conclusion.,Almotriptan provides relief from migraine-associated symptoms of nausea, vomiting, photophobia, and phonophobia, and thus represents an attractive treatment option for a wide spectrum of migraine symptomatology. [source] Daytime pharmacodynamic and pharmacokinetic evaluation of low-dose sublingual transmucosal zolpidem hemitartrateHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2008Thomas Roth Abstract Objectives Buffered low-dose sublingual transmucosal zolpidem lozenge hemitartrate (ST zolpidem) is being developed for the treatment of middle-of-the-night insomnia. The objective of this double-blind placebo-controlled cross-over study (n,=,24) was to evaluate the pharmacokinetics (PK) and daytime-sedative profile of 1.0, 1.75, and 3.5,mg dose of the formulation. Methods Daytime sedation was measured pre-dose and up to 5,h post-dose objectively by the Digit Symbol Substitution Test (DSST) and subjectively using the Visual Analog Scale (VAS). Blood samples for PK assessment was collected pre-dose and up to 12,h post-dose. Results The 1.75 and 3.5,mg, but not the 1,mg, ST zolpidem produced significant sedation versus placebo within 20,min of dosing which lasted for up to 3,h. Zolpidem from the formulation was rapidly absorbed and reached maximum plasma concentrations within 38,min of dosing, however the half-life was independent of the dose and side effects were consistent with the known pharmacology of the drug. Conclusions ST zolpidem produced rapid, short duration of sedation and the effect was consistent with its PK profile. This novel low-dose formulation of zolpidem may provide clinicians and patients with a prn option for the management of sleep maintenance insomnia. Copyright © 2007 John Wiley & Sons, Ltd. [source] Modafinil and nicotine interactions in abstinent smokersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2008Mehmet Sofuoglu Abstract In this study, we examined the effects of a wakefulness-promoting medication, modafinil, alone and with the nicotine lozenge, on subjective, physiological and cognitive measures as well as on nicotine withdrawal in overnight abstinent cigarette smokers. Nineteen smokers, 13 male and 6 female, participated in a double-blind, placebo-controlled, crossover study. In each of three experimental sessions, subjects were treated orally with a single 200,mg or 400,mg dose of modafinil or placebo. Two hours and 10 min following the medication treatment, subjects received a single 2,mg nicotine lozenge. Both doses of modafinil alone increased the rating of elated-depressed on the Profile of Mood States (POMS) subscale in the direction of depressed and increased ratings of negative affect on the Positive and Negative Affect Schedule (PANAS). In contrast, the 200,mg modafinil dose combined with a 2,mg nicotine lozenge, increased the rating of energetic-tired in the direction of energetic on the POMS subscale. Modafinil attenuated self-reported rating of ,drug strength' in response to the nicotine lozenge. Modafinil, alone or in combination with the nicotine lozenge, did not affect tobacco withdrawal symptoms. There was an increase in baseline heart rate and systolic blood pressure under modafinil treatment. In addition, modafinil speeded reaction times on a modified Stroop task. The clinical utility of modafinil for smoking cessation needs to be determined in future studies. Copyright © 2007 John Wiley & Sons, Ltd. [source] Dose-response effects of zaleplon as compared with triazolam (0·25 mg) and placebo in chronic primary insomniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2000Christopher L Drake Abstract The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0·25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0·25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0·25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0·25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0·25 mg) produced increases in total sleep time (,25 min) and decreases in latency to persistent sleep at a dose of 0·25 mg. Copyright © 2000 John Wiley & Sons, Ltd. [source] Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptanINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 12 2008L. C. Newman Summary Aims:, To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. Methods:, Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. Results:, More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. Conclusion:, Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure. [source] First-dose success with vardenafil in men with erectile dysfunction and associated comorbidities: RELY-IINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2006L. VALIQUETTE Summary First-dose success of phosphodiesterase type 5 (PDE5) inhibitors may be adversely affected in patients with comorbidities. This article reports first-dose success rates for vardenafil 10 mg in men with erectile dysfunction (ED) and associated comorbidities who participated in the challenge phase of the Reliability , Vardenafil for Erectile Dysfunction I study. This study involved an open-label, single-dose, 1-week challenge period where patients who achieved SEP-2 (penetration) success were randomised to vardenafil 10 mg or placebo for 12 weeks in a double-blind manner. The first-dose success rates for SEP-2 and SEP-3 (maintenance of erection to completion of intercourse) were stratified according to comorbidities. Safety was assessed using adverse events (AEs). Of 600 men who received a single 10 mg dose of vardenafil, 32% had hypertension, 16% had diabetes and 19% had dyslipidaemia. Vardenafil demonstrated overall effectiveness, including first-dose SEP-2 and SEP-3 success rates in patients with and without specific comorbidities. Initial overall success rates for SEP-2 and SEP-3 during the challenge phase were 87% and 74% respectively. First-dose SEP-2 and SEP-3 success rates were 84% and 66% in men with hypertension (n = 191); 84% and 72% in men with dyslipidaemia (n = 116); and 75% and 58% in men with diabetes (n = 95). Vardenafil was well tolerated and most AEs, including the most frequently reported flushing (3.5%), were mild to moderate in intensity. Vardenafil 10 mg is generally well tolerated and efficacious, providing first-dose success with a consistently high rate of reliability of penetration and maintenance of erection in men with ED and associated comorbidities. [source] The therapeutic profile of zolmitriptan in clinical practiceINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2004H.C. Diener Summary The efficacy and tolerability of the 5-HT1B/1D -receptor agonist zolmitriptan was evaluated in an open post-marketing surveillance study in 12,919 patients, treating 36,510 migraine attacks. Mean visual analogue scale scores for pain decreased (6.9,2.2; 68% improvement) and scores for impairment of normal activities decreased (6.6,2.2; 67% improvement) at 2 h after dose. Non-headache symptoms of migraine resolved in 73,86% of attacks. Improvement was achieved within 2 h in >80% of attacks and within 1 h in 37% of attacks. This high level of efficacy was achieved with a single 2.5 mg dose in 95% of attacks. Compared with previous migraine treatments, 85% of patients preferred zolmitriptan for efficacy and 56% for better tolerability. Corresponding preference rates were 87 and 63% when compared with ergot alkaloids. Adverse events occurred in 2% of patients and were either typical class effects or known symptoms and complications of migraine. These results provide evidence for the high efficacy and good tolerability of the 2.5 mg dose of zolmitriptan in clinical practice in migraine. Zolmitriptan was very well tolerated, with patients expressing a distinct preference for zolmitriptan over previous treatments. [source] Allergic contact dermatitis to mango fleshINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2004Sari Weinstein MD A 22-year-old white female student presented to the Emergency Department with a 2-day history of patchy pruritic erythema of the face, neck, and arms with periorbital edema. The eruption began as an isolated patch of nasal erythema, with subsequent extension to involve the entire face. Within 2 days, fine pinpoint papules were noted on the face, anterior chest, neck, and upper extremities. Periorbital edema was present without intraoral abnormalities or laryngeal changes. An erythematous, mildly lichenified plaque was noted on the ventral left wrist. The past medical history was significant for two similar, milder episodes of allergic reactions of uncertain etiology occurring within the previous 2 months. The previous eruptions resolved after treatment with oral loratodine and topical fluocinonide cream 0.05%. The patient denied any history of contact urticaria or new household or personal hygiene contactants, although she did report frequent ingestion of peeled mangoes. Her brother had a history of eczematous dermatitis. In the Emergency Department, the patient was administered intravenous diphenhydramine and a single 50 mg dose of oral prednisone. She continued treatment with a 5-day course of prednisone, 50 mg daily, with loratodine, 20 mg daily, and diphenhydramine as needed; however, no symptomatic improvement was seen over 4 days. She was then advised to restart fluocinonide cream twice daily. Patch testing was performed to the North American Contact Dermatitis Group Standard Series utilizing methods of the International Contact Dermatitis research group with Finn chambers. Mango skin and mango flesh harvested 5 mm below the skin surface were also placed in duplicate and tested under Finn chambers. Positive (1+) reactions were noted to nickel and p -tertbutylphenol formaldehyde resin, and bullous reactions were found to mango skin and surface flesh in duplicate (Fig. 1). Complete avoidance of mango led to resolution of the initial eruption. The clinical relevance of nickel and p -tertbutylphenol formaldehyde resin was thought to be associated with the wrist lesion immediately below a glued portion of a wristwatch strap and metal clasp. Figure 1. Positive patch test reactions, in duplicate, to mango skin (left column) and mango flesh 5 mm below the skin (right column) [source] Olanzapine versus placebo in the treatment of psychosis with or without associated behavioral disturbances in patients with Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 2 2004Peter Paul De Deyn Abstract Objectives Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings. Methods Patients (n,=,652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5,mg/day). Results Mean age was 76.6±10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items,primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5,mg olanzapine group (,6.2,±,4.9) was significantly greater than with placebo (,5.0,±,6.1, p,=,0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz,2.5 olanzapine group (2.8,±,1.4, p,=,0.030) relative to placebo (3.2,±,1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol. Conclusions While 1.0,mg olanzapine did not show significant differences from placebo, the 2.5,mg dose was a reasonable starting dose. Olanzapine at 7.5,mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated. Copyright © 2004 John Wiley & Sons, Ltd. [source] Safety and therapeutic efficacy of undenatured type-ii collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2009R. C. Gupta Osteoarthritis (OA) is the most common form of arthritis, which causes severe inflammation and loss of cartilage. It is a debilitating disease that commonly affects thousands of horses each year. Recently, we assessed the anti-arthritic and anti-inflammatory potential of undenatured type II collagen (UC-II) in horses. This comparative investigation evaluated arthritic pain in horses receiving daily placebo, UC-II 320 mg/day (providing 80 mg active UC-II), 480 mg/day (providing 120 mg active UC-II), or 640 mg/day (providing 160 mg active UC-II), and glucosamine and chondroitin (5.4 g/day and 1.8 g/day, respectively, bid for the first month, and thereafter once daily) for 150 days. Pain in each leg was evaluated using the flexion test and the lameness-grading system after the initial two strides. Average pain of all four legs represented the pain for each horse. Horses receiving placebo showed no change in arthritic condition, while those receiving 320, 480, or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 mg dose provided optimal effects. With this dose, reduction in overall pain was from 5.7 ± 0.0.42 (100%) to 0.7 ± 0.42 (12%); and in pain upon limb manipulation from 2.35 ± 0.37 (100%) to 0.52 ± 0.18 (22%). In regards to glucosamine and chondroitin treated group, although reduction in pain was significant compared to pretreated values, the efficacy was significantly less compared with that observed with UC-II. UC-II was found to be twice as effective as glucosamine and chondroitin in arthritic horses. Clinically, physical condition, and liver (ALP, GGT, and bilirubin), kidney (BUN and creatinine), and heart (CK) functions remained unchanged, suggesting that these supplements were well tolerated. Overall, these results demonstrate that UC-II was significantly more efficacious than glucosamine and chondroitin in arthritic horses. [source] Adding Gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplastyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009H. CLARKE Background: Gabapentin (GPN) is effective in reducing post-operative pain and opioid consumption, but its effects with regional anesthesia for total hip arthroplasty (THA) are not known. We designed this study to determine whether (1) gabapentin administration reduces pain and opioid use after THA using a multimodal analgesic regimen including spinal anesthesia; (2) pre-operative administration of gabapentin is more effective than post-operative administration. Methods: After REB approval and informed consent, 126 patients were enrolled in a double-blinded, randomized-controlled study. Patients received acetaminophen 1 g per os (p.o.), celecoxib 400 mg p.o. and dexamethasone 8 mg intravenously, 1,2 h pre-operatively. Patients were randomly assigned to one of three treatment groups (G1: Placebo/Placebo; G2: GPN/Placebo; G3: Placebo/GPN). Patients received gabapentin 600 mg (G2) or placebo (G1 and G3) 2 h before surgery. All patients had spinal anesthesia [15 mg (3cc) of 0.5% hypobaric bupivacaine with 10 ,g of fentanyl]. In the post-anesthetic care unit, patients received gabapentin 600 mg (G3) or placebo (G1 and G2). On the ward, patients received acetaminophen 1000 mg p.o. q6h, celecoxib 200 mg p.o. q12h and a morphine PCA device. Patients were interviewed 6 months post-surgery to determine the incidence and severity of chronic post-surgical pain. Results: Mean±SD cumulative morphine (mg) consumption (G1=49.4±24.8, G2=47.2±30.1 and G3=56.1±38.2) at 48 h and pain scores at 12, 24, 36 and 48 h post-surgery were not significantly different among the groups [G1 (n=38), G2 (n=38) and G3 (n=38)]. Side effect profiles were similar across groups. Six months after surgery, the number of patients who reported chronic post-surgical pain (G1=10, G2=12 and G3=9) and the severity of the pain (G1=4.2±2.9, G2=4.1±2.2 and G3=4.9±2.2) did not differ significantly among the groups (P>0.05). Conclusions: A single 600 mg dose of gabapentin given pre-operatively or post-operatively does not reduce morphine consumption or pain scores in hospital or at 6 months after hip arthroplasty within the context of spinal anesthesia and a robust multimodal analgesia regimen. [source] Smoking behaviour modulates pharmacokinetics of orally administered clopidogrelJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008A.-M. Yousef PhD Summary Background and objectives:, Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. Methods:, Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0,,). Results:, One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC0,, (smokers: 6·24 ± 2·32 ,g/h/mL vs. non-smokers: 8·93 ± 3·80 ,g/h/mL, P < 0·001) and shorter half-life (smokers: 5·46 ± 2·99 vs. non-smokers: 8·43 ± 4·26, P = 0·001). Smoking behaviour had no influence on Cmax (P = 0·3) and Tmax (P = 0·7). There was no statistically significant difference in Cmax, AUC0,,, Tmax and t1/2e between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean ± SE; 26·93 ± 0·16 vs. 23·11 ± 0·27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (Cmax = 3·09 ± 0·99 ,g/mL, CV = 32%), (Tmax =0·76 ± 0·24 h, CV = 31·6%), (AUC0,, = 7·98 ± 3·58 ,g/h/mL, CV = 44·8%), and (t1/2e = 7·38 ± 4·10 h, CV = 55·6%). Conclusion:, Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed. [source] Ticlopidine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2004Application to bioequivalence study Abstract A rapid, sensitive and specific method to quantify ticlopidine in human plasma using clopidogrel as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid,liquid extraction using diethyl ether,hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C8 4 µm analytical column (150 × 4.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 1.0,1000 ng ml,1 (r2 > 0.999427). The limit of quantification was 1.0 ng ml,1. This HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250 mg tablet formulations (ticlopidine test formulation from Apotex do Brasil, Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A single 250 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for Cmax and area under the curve ratios were all inside the 80,125% interval proposed by the US Food and Drug Administration, it was concluded that ticlopidine formulation from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both the rate and the extent of absorption. Copyright © 2004 John Wiley & Sons, Ltd. [source] Bioavailability and pharmacokinetic model for ritonavir in the ratJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2007R. Lledó-García Abstract The aim of this study is to investigate in vivo the oral bioavailability of ritonavir and to evaluate the pharmacokinetic model that best describes the plasma concentration behavior after oral and intravenous administration. Male Wistar rats were intravenously administered at 3 mg dose of pure ritonavir and oral administered at 4.6,±,2.5 mg of diluted Norvir®. Blood samples were taken by means of the jugular vein for a 24 h period of time. An analytical high-performance liquid chromatography (HPLC) technique was developed in order to quantify ritonavir plasma concentrations. A nonlinear modeling approach was used to estimate the pharmacokinetic parameters of interest. Results showed that a two-compartmental model with zero-order kinetic in the incorporation process of ritonavir into the body better fitted intravenous and oral data. The estimated oral bioavailability by means of noncompartmental and compartmental approaches resulted in 74% and 76.4%, respectively. These values confirm the ones obtained by other authors in the rat. In conclusion, a zero-order kinetic in the incorporation process at the administered doses suggests the saturation of the possible specialized transport mechanisms involved in the incorporation of ritonavir into the body. These results could justify the use of low doses of ritonavir when improving the bioavailability of other protease inhibitors (PIs) is required. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] Mediastinal node and diaphragmatic targeting after intracavitary injection of avidin/99mTc-blue-biotin-liposome systemJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2006Luis A. Medina Abstract A method for delivering drugs to sites of disease extension in mediastinal nodes is described. Mediastinal node and lymphatic distributions were determined after intracavitary injection of the avidin/biotin-liposome system in normal rats. The effect of the injected dose on lymphatic targeting of liposomes after intraperitoneal injection of 99mTc-blue-biotin-liposomes and intrapleural injection of avidin, and vice versa, is presented. Scintigraphic imaging was used to follow the movement of 99mTc-blue-biotin-liposomes to determine the pharmacokinetics and organ uptake. Tissue biodistribution studies were performed 22 h after injection of the 99mTc-blue-biotin-liposomes. Results indicated that independent of the cavity in which each agent was injected, a dose of 5.0 mg of each agent results in higher mediastinal node targeting (8%,10% ID/Organ) as compared with the injection of a 0.5 mg dose (2%,5% ID/Organ, p,<,0.05). Targeting of diaphragm and associated lymphatics was observed when 99mTc-blue-biotin-liposomes were injected in peritoneum and avidin in pleural space. In contrast, pleural, and pericardial lymphatic targeting was observed when 99mTc-blue-biotin-liposomes were injected in pleural space and avidin in peritoneum. Intracavitary injection of the avidin/biotin-liposome system could potentially be used for the delivery of prophylactic drugs that could reduce tumor metastasis and infection spread to mediastinal nodes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:207,224, 2006 [source] The detection and quantification of lorazepam and its 3- O -glucuronide in fingerprint deposits by LC-MS/MSJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2009Edward Goucher Abstract The use of fingerprints as an alternative biological matrix to test for the presence of drugs and/or their metabolites is a novel area of research in analytical toxicology. This investigation describes quantitative analysis for the benzodiazepine lorazepam and its 3- O -glucuronide conjugate in fingerprints following the oral administration of a single 2 mg dose of lorazepam to five volunteers. Creatinine was also measured to investigate whether the amount of drug relative to that of creatinine would help to account for the variable amount of secretory material deposited. Fingerprints were deposited on glass cover slips and extracted by dissolving them in a solution of dichloromethane/methanol, containing tetradeuterated lorazepam as an internal standard. The samples were evaporated, reconstituted with mobile phase and analysed by LC-MS/MS. Chromatography was achieved using an RP (C18) column for the analysis of lorazapem and its glucuronide, and a hydrophilic interaction column (HILIC) for the analysis of creatinine. Lorazepam and its glucuronide were only detected where ten prints had been combined, up to 12 h following drug administration. In every case, the amount of lorazepam glucuronide exceeded that of lorazepam, the peak amounts being 210 and 11 pg, respectively. Adjusting for creatinine smoothed the elimination profile. To our knowledge, this represents the first time a drug glucuronide has been detected in deposited fingerprints. [source] Automated determination of venlafaxine in human plasma by on-line SPE-LC-MS/MS.JOURNAL OF SEPARATION SCIENCE, JSS, Issue 4 2009Application to a bioequivalence study Abstract A new automated SPE-LC-ESI-MS/MS method was developed and validated to quantify venlafaxine in human plasma using fluoxetine as an internal standard. The analytes were automatically extracted from plasma by C18 SPE cartridges, separated on a C8 RP column and analyzed by MS in the multiple reaction-monitoring (MRM) mode. The method has a chromatographic run time of 4.0 min and a linear calibration curve over the range of 0.25,200 ng/mL (r >0.997). The between-run precisions, based on the percent RSD for replicate quality controls (0.75; 80, and 200 ng/mL), were < 8.5% for all concentrations. The between-run accuracies, based on the percent relative error, were < 4.0%. This method was successfully employed in a bioequivalence study of two venlafaxine capsule formulations (test formulation from Eurofarma (Brazil) and Efexor XR, reference formulation, from Wyeth-Whitehall, Brazil) in 48 healthy volunteers of both sexes who received a single 150 mg dose of each formulation. More than 3000 samples were analyzed eliminating the analyst's exposure to hazardous organic solvents normally employed in off-line liquid,liquid extractions. The 90% confidence interval (CI) of the individual ratio geometric mean for Test/Reference was 91.6,103.4% for AUC0,48 h and 102.2,112.6% for Cmax. Since both 90% CI for AUC0,48 h and Cmax were included in the 80,125% interval proposed by the US Food and Drug Administration (FDA) and the Brazilian National Health Surveillance Agency (ANVISA), the test formulation was considered bioequivalent to Efexor XR according to both the rate and extent of absorption. [source] Efficacy of oral rofecoxib versus intravenous ketoprofen as an adjuvant to PCA morphine after urologic surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2004M. C. Cabrera Background:, Adjunctive use of nonsteroidal anti-inflammatory drugs has become increasingly popular in the perioperative period because of their opioid-sparing effects. This randomized, controlled, double-dummy study was designed to evaluate the cost-effectiveness of using oral rofecoxib as an alternative to intravenous ketoprofen for pain management in patients undergoing urologic surgery. Methods:, Seventy patients were randomly assigned to receive either a placebo (Control) or rofecoxib 50 mg po (Rofecoxib) 1 h prior to surgery. After a standardized spinal anesthetic, patients in the Control group received ketoprofen 100 mg IV q 8 h for 24 h, while the Rofecoxib group received an equivolume of saline at 8-h intervals for 24 h. Both groups were allowed to self-administer morphine (1 mg IV boluses) using a PCA delivery system. The need for ,rescue' analgesic medication, as well as pain scores [using an 11-point verbal rating scale (VRS) (0 = none to 10-severe)], were recorded at 1, 2, 6, 12, and 24-h intervals after surgery. In addition, the incidences of side-effects were recorded at the end of the study period. Results:, Total amount of morphine required in the initial 24-h postoperative period was nonsignificantly reduced in the Rofecoxib group (29 ± 2 vs. 37 ± 4 mg). More importantly, the percentage of patients reporting moderate-to-severe pain (VRS score ,4) during the study period was lower in the Rofecoxib group (12 vs. 22%, P < 0.05). The daily cost of rofecoxib (USD 1.14 for 50-mg dose) was also significantly less than ketoprofen (USD 3.06 for three 100-mg doses). Conclusion:, Premedication with oral rofecoxib (50 mg) is a cost-effective alternative to the parenteral nonselective NSAID, ketoprofen (100 mg q 8 h), when used as an adjuvant to PCA morphine for pain management after urologic surgery. [source] Incidence of side-effects associated with high-dose ferric gluconate in patients with severe chronic renal failureNEPHROLOGY, Issue 1 2003BAHAR BASTANI SUMMARY: Ferric gluconate complex in sucrose (FerrlecitÔ) has been associated with less side-effects than iron dextran; however, the recommended dose of 62.5,125 mg per treatment is only suitable for haemodialysis (HD) patients. We retrospectively analysed the incidence of the side-effects associated with a high dose of FerrlecitÔ infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3,4 h, and 10 treatments of 500 mg/5 h infusion). The patients were in the age range of 32,75 years old, seven with chronic renal failure (CRF), and six on dialysis treatment. One (10%) of the 10 treatments using a 250 mg dose was complicated with severe nausea/vomiting, diarrhoea and a burning sensation in the feet. Three (30%) of the 10 treatments using a 500 mg dose were complicated with: chills, severe nausea/vomiting, hypotension and syncope in one; severe nausea/vomiting, diarrhoea and hypotension in one; and an episode of vomiting in one patient. A single treatment with a 250 mg dose resulted in no significant change in haematological parameters. A single treatment with a 500 mg dose resulted in a significant increase in haemoglobin (Hgb) and haematocrit (Hct), but only a rising trend in serum iron,% transferrin saturation and ferritin pre versus 1,2 months postinfusion. In conclusion, FerrlecitÔ doses of 250 or 500 mg are complicated with significant untoward reactions in 10,30% of patients, in a dose-dependent fashion. [source] Novel pharmacology: asimadoline, a ,-opioid agonist, and visceral sensationNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008M. Camilleri Abstract, Asimadoline is a potent ,-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the , receptor, with IC50 of 5.6 nmol L,1 (guinea pig) and 1.2 nmol L,1 (human recombinant), and high selectively with , : , : , binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in irritable bowel syndrome (IBS) patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 h post- on-demand treatment with asimadoline was not significantly reduced. Post hoc analyses suggest that asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date. [source] Albendazole: Single or Combination Therapy with Permethrin against Pediculosis CapitisPEDIATRIC DERMATOLOGY, Issue 2 2006Ciler Akisu M.D. In the present study, we investigated whether albendazole could be used in the treatment of pediculosis capitis in combination with 1% permethrin or alone. A total of 150 children were randomly divided to five groups of 30 each. Group 1 got albendazole in a single dose (400 mg), group 2 got albendazole at 400 mg for 3 days, group 3 was given 1% permethrin, group 4 took 1% permethrin and albendazole in a single dose (400 mg), and group 5 got 1% permethrin and albendazole in a dose of 400 mg for 3 days. Groups given albendazole were also given another 400 mg dose of albendazole after 1 week. The success rate of treatment at the 2-week follow-up for all groups was 61.5%, 66.6%, 80.0%, 84.6%, and 82.1%, respectively. No statistically significant difference was found between the groups. The results of this study suggest that albendazole is effective against pediculosis capitis and there is no synergistic effect between albendazole and 1% permethrin. [source] Exhaled nitric oxide after a single dose of intramuscular triamcinolone in children with difficult to control asthmaPEDIATRIC PULMONOLOGY, Issue 7 2007Jayachandran R Panickar MRCPCH Abstract In a previous study, we reported that intramuscular (IM) triamcinolone improves symptoms in children with difficult asthma. In 2005, we revised our difficult asthma protocol to include assessment of airway inflammation, both directly using sputum induction and indirectly by measurement of exhaled nitric oxide (eNO). In this retrospective review, we aimed to describe (i) the changes in eNO and symptoms after a single 60 mg dose of IM triamcinolone and (ii) the changes in inflammatory markers in the subgroup with non-eosinophilic asthma (i.e., an induced sputum eosinophil differential count <2.0%). Seven children received IM triamcinolone during the study period. In all children, symptom scores fell in the week following the IM injection (P,<,0.01 vs. the pre-treatment week), and remained reduced for up to 6 weeks. eNO also fell within a week after IM therapy (P,<,0.01), and remained reduced for up to 4 weeks. Non-eosinophilic asthma was definitively identified in three children, and in this group, eNO and symptoms fell after the IM injection. We conclude that IM triamcinolone therapy reduces both eNO and symptoms for up to 4 weeks in children with difficult asthma. Our data provide preliminary evidence that IM triamcinolone is an effective anti-inflammatory therapy in children with induced sputum non-eosinophilic asthma. Pediatr Pulmonol. 2007; 42:573,578. © 2007 Wiley-Liss, Inc. [source] Novel tobramycin inhalation powder in cystic fibrosis subjects: Pharmacokinetics and safetyPEDIATRIC PULMONOLOGY, Issue 4 2007David E. Geller MD Abstract Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy. We evaluated the pharmacokinetics (PK) and safety of tobramycin inhalation powder (TIP), a novel dry-powder formulation designed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections. This was a multi-center, open-label, sequential-cohort, single-dose, dose-escalation study using the standard 300 mg dose of tobramycin solution for inhalation (TSI) as an active control. Subjects were randomized to TIP or TSI in a 3:1 ratio in each of five cohorts. Measurements included serum and sputum tobramycin concentrations, administration time, serum chemistries, acute change in lung function, and adverse events (AEs). Out of 90 randomized subjects, 86 had data for safety analysis; and 84 had data for PK analysis. Serum tobramycin PK profiles were similar for TIP and TSI. Four capsules of 28 mg TIP (total tobramycin dose 112 mg) produced comparable systemic exposure to 300 mg TSI, in less than one-third the administration time. The most common AEs associated with TIP were cough (20%) and dysgeusia (17%). TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation. The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation. The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections. Pediatr Pulmonol. 2007; 42:307,313. © 2007 Wiley-Liss, Inc. [source] Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2004Darren M. Ashcroft PhD Abstract Objective To evaluate the comparative efficacy and tolerability of naratriptan in the treatment of acute attacks of migraine. Design Meta-analysis of randomised controlled trials using a random effects model. Subjects A total of 4499 patients suffering from moderate or severe attacks of acute migraine reported in ten trials. Main outcome measures Response rate ratios for headache relief, pain-free response and sustained relief (4,24 hours). Adverse events were estimated with the rate ratio (RR), risk difference and number needed to harm. Results Pooled RRs relative to placebo for pain-free response at 2 and 4 hours for naratriptan 2.5,mg were 2.52 (95%,CI: 1.78,3.57) and 2.58 (1.99,3.35). Naratriptan 2.5,mg was more effective than naratriptan 1,mg; the corresponding RRs for pain-free response at 2 and 4 hours were 1.54 (95%,CI: 1.28,1.86) and 1.35 (1.20,1.51). In contrast, naratriptan 2.5,mg was less effective in pain-free response than either rizatriptan 10,mg at 4,hours (RR: 0.68; 95%,CI: 0.55,0.85) or sumatriptan 100,mg at 4,hours (RR: 0.79; 95%,CI: 0.67,0.93). However, significantly fewer patients experienced adverse effects with naratriptan 2.5,mg than with rizatriptan 10,mg (RR: 0.73; 95%,CI: 0.56,0.97) or sumatriptan 100,mg (RR: 0.68; 95%,CI: 0.55,0.86). Conclusions Naratriptan is an effective and well-tolerated treatment for acute attacks of migraine. Head-to-head comparisons suggest that naratriptan 2.5,mg is significantly more effective than the 1,mg dose. Rizatriptan 10,mg and sumatripatn 100,mg were superior to naratriptan in terms of headache relief, while zolmitriptan 2.5,mg seemed to have comparable efficacy. Randomised controlled trials have shown that at licensed doses (1 and 2.5,mg), naratriptan is associated with a lower incidence of adverse effects than rizatriptan, sumatriptan and zolmitriptan. The incidence rates of adverse effects were similar to placebo. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patientsPHYTOTHERAPY RESEARCH, Issue 9 2009Smita Pattanaik Abstract Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability-enhancer. The present study aimed at evaluating the effect of piperine on the steady-state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t -test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC0-12hr (p < 0.001), average Css (p < 0.001), t1\2el (p < 0.05) and a decrease in Kel (p < 0.05), in both the dose groups, whereas changes in Ka and t1\2a were not significant. Cmax (p < 0.01) and tmax (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption. Copyright © 2009 John Wiley & Sons, Ltd. [source] Anxiolytic effects of a combination of Melissa ofcinalis and Valeriana ofcinalis during laboratory induced stressPHYTOTHERAPY RESEARCH, Issue 2 2006David O. Kennedy Abstract Objective: Melissa ofcinalis (lemon balm) and Valeriana ofcinalis (valerian) have been used both traditionally and contemporaneously as mild sedatives, anxiolytics and hypnotics. Recent research has suggested that both may attenuate laboratory induced stress. As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory-induced stress. Methods: In this double-blind, placebo-controlled, randomized, balanced cross-over experiment, 24 healthy volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing M. ofcinalis and V. ofcinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. Modulation of mood and anxiety were assessed during pre-dose and 1 h, 3 h and 6 h post-dose completions of a 20 min version of the Dened Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed. Results: The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety. However, the highest dose (1800 mg) showed an increase in anxiety that was less marked but which reached signicance during one testing session. In addition, all three doses led to decrements in performance on the Stroop task module within the battery, and the two lower doses led to decrements on the overall score generated on the DISS battery. Conclusions: These results suggest that a combination of Melissa ofcinalis and Valeriana ofcinalis possesses anxiolytic properties that deserve further investigation. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||