			Home About us Contact

Oral Route (oral + route)

Distribution by Scientific Domains

Medical Sciences	75%
Life Sciences	9%
3 Other Domains	16%

Distribution within Medical Sciences

Allergy & Clinical Immunology	12%
Pediatrics	8%

Selected Abstracts

Poppy seed tea and opiate abuse in New Zealand

DRUG AND ALCOHOL REVIEW, Issue 2 2007
KLARE BRAYE
Abstract The opium poppy Papaver somniferum contains an array of opiates. There is a variety of methods of preparation that can be used by people with opiate dependence, with patterns of use determined by numerous factors including cost, safety, potency and legal status. The objective of this study was to determine the frequency and nature of poppy seed tea (PST) use by opiate-dependent patients in the form of a written questionnaire. The study took place at the Community Alcohol and Drug Clinic, Wellington, New Zealand, and comprised 24 opiate-dependent patients attending the clinic. A total of 11 of 24 (46%) patients reported having used PST. In five patients currently using PST it represented the major source of opiates, and two had managed to withdraw from use of other opiates with regular PST use. Patients reported a median onset of action of 15 minures and an effect lasting a median of 24 hours. The major limitation of PST use was the foul taste. PST is used commonly by opiate-dependent patients attending an alcohol and drug clinic in New Zealand. The use of PST as the major source of opiates could be considered favourably within ,harm reduction' philosophies, because of its low cost, legal availability and oral route of administration. Conversely, there is the potential for PST to act as a ,gateway drug' by inducing opioid dependence and introducing people to the culture of drug abuse. [source]

Rectal Absorption of Lamotrigine Compressed Tablets

EPILEPSIA, Issue 7 2000
Angela K. Birnbaum
Summary: Purpose: Interruption of oral drug administration poses a significant clinical problem for antiepileptic drugs that have no parenteral formulation. If a drug is absorbed rectally, rectal administration can be a useful alternative when the oral route of administration is not possible. The purpose of this study was to compare the single-dose pharmacokinetics of la-motrigine (LTG) compressed tablets after rectal and oral administration in healthy volunteers. Methods: A single LTG compressed tablet (100 mg) was administered orally and rectally to 12 volunteers in this single-dose, two-period, crossover study with a 2-week washout between doses. For rectal administration, tablets were crushed and suspended in 10 mL of water. Plasma samples were collected from 0 to 120 hr after each dose and analyzed for LTG by an HPLC method developed for this investigation. Results: LTG plasma concentrations were lower after rectal administration versus oral administration. The average area under the curve was 28.90 ± 9.5 ,g/mL/hr after rectal administration and 51.71 ± 19.2 ,g/mL/hr after oral administration. The average maximum LTG concentration was 0.53 ± 0.14 ,g/mL after rectal administration and 1.45 ± 0.35 ,g/mL after oral administration. The relative bioavailability for LTG compressed tablets was 0.63 ± 0.33 for rectal administration. There were no drug-related rashes or serious side effects. Conclusions: LTG suspension prepared from LTG compressed tablets is absorbed rectally, although not to the same extent or rate as when given orally. [source]

Effect of Losartan on Sodium Appetite of Hypothyroid Rats Subjected to Water and Sodium Depletion and Water, Sodium and Food Deprivation

EXPERIMENTAL PHYSIOLOGY, Issue 5 2001
D. Badauê-Passos Jr
The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg g,1, the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg g,1 did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors. [source]

Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2009
C. Girish
Abstract Oxidative stress is implicated as a common pathologic mechanism contributing to the initiation and progression of hepatic damage in a variety of liver disorders. Present study attempts to evaluate the hepatoprotective activity of picroliv, curcumin and ellagic acid in comparison to silymarin using paracetamol (PCM) induced acute liver damage. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg) and was assessed by quantifying the serum enzyme activities, phenobarbitone induced sleeping time and histopathological analysis of liver tissues. The antioxidant parameters, malondialdehyde (MDA), reduced glutathione (GSH) and catalase of the liver tissue were also assessed. The herbal drugs were administered for 7 days by oral route at 50 and 100 mg/kg. PCM induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (alanine transaminase, aspartate transaminase and alkaline phosphatase) in serum and MDA level in liver. There was also a significant decrease in activity of GSH and catalase levels. The histopathological examination on toxic models revealed centrizonal necrosis and fatty changes. Pretreatment of mice with picroliv, curcumin and ellagic acid reversed these altered parameters towards normal values, which were compared with silymarin. The normalization of phenobarbitone induced sleeping time suggests the restoration of liver cytochrome P450 enzymes. This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing the lipid peroxidation and augmenting the antioxidant defense system or regeneration of hepatocytes. These active phytochemicals may be developed as drugs for the treatment of liver diseases. [source]

Role of topical and nutritional supplement to modify the oxidative stress,

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 6 2002
P. Morganti
Synopsis Background: Evidence suggests that signs of skin ageing such as wrinkling, ragging and actinic lentigines, may be connected to cumulative oxidative damage incurred throughout our lifetimes. To counteract this oxidative injury, skin is equipped with a network on enzymatic and non-enzymatic antioxidant systems, such as tocopherols, ascorbate polyphenols. All these compounds administered topically by cosmetics or by oral route by diet supplements, have been shown to exert an antioxidant/protective effect in skin or skin cells. Objective: The object of this study was to evaluate both in vitro and in vivo the activity performed by different topical antioxidants and nutritional supplements. Methods: A randomized double-blind placebo-controlled study was carried out for 8 weeks on 30 dry-skinned elderly volunteers, women aged between 48 and 59 years, with moderate xerosis and photoageing. Surface skin lipids, skin hydration and MDA determination were topically detected by 3C System. ROS was evaluated on the blood serum and on IL-3 stimulated human leukocytes by ROS Meter System at 505 nm. All the subjects applied twice a day for 2 months a nanocolloidal gel and/or take a diet supplement by oral route at the quantity of two capsules per day. All the formulations used were antioxidant-enriched (ascorbic acid, tocopherol, alpha-lipoic acid, melatonin, emblica). Results: Oxidative stress and consequently lipids peroxidation decreased from 30 to 40% (P < 0.005) in blood serum of all the subjects treated with antioxidant compounds topically and by oral route. Both free radicals recovered in blood serum and on skin (in vivo) and ROS induced by irradiation of leucocytes with UVB light (in vitro), appear sensibly lower in subjects antioxidant-treated. Conclusions: From the obtained data, it seems possible to conclude that all the compounds used play interesting role as topical and systemic photoprotectants, thanks to their interesting antioxidant property. Moreover, the antioxidant treatment seems to be a promising therapeutic approach also in reducing the oxidative stress of people affected by photoaging. Résumé Les faits semblent montrer que les signes du vieillissement cutané tels que les rides, la perte d'élasticité ou les taches de vieillesse, peuvent être liés aux effets oxydants cumulés subis tout au long de la vie. Pour contrer ces effets oxydants, la peau est équipée d'un réseau de systèmes antioxydants enzymatiques et non enzymatiques tels que les tocophérols, l'ascorbate et les polyphénols. Tous ces composés, administrés par voie topique par des cosmétiques ou par voie orale avec des suppléments alimentaires, se sont révélés exercer un effet antioxydant/protecteur sur la peau ou les cellules de la peau. L'objet de cette étude était d'évaluer aussi bien in-vitro qu'in-vivo l'activité de différents antioxydants topiques et suppléments alimentaires. Une étude randomisée contre placebo en double aveugle a été conduite sur 8 semaines avec 30 volontaires,gés à peau sèche, des femmes de 48 à 59 ans, présentant une xérose et un viellissement modéré. Les lipides à la surface de la peau, l'hydratation de la peau et la MDA ont été suivis de façon topique par le SYSTEM 3 C. Les ROS (Reactive Oxygen Species) ont été déterminés dans le sérum sanguin et sur les leucocytes humains 12-3 stimulés par un SYSTEM ROS-METER à 505 nm. Tous les sujets ont appliqué deux fois par jour pendant deux mois un gel nanocolloïdal et/ou pris des suppléments alimentaires par voie orale à raison de deux gélules par jour. Toutes les formulations utilisées étaient enrichies en antioxydant (acide ascorbique, tocophérol, acide alpha-lipoïque, mélatonine, emblica). Le stress oxydant et par conséquent la péroxydation des lipides diminue de 30 à 40% (p < 0.005) dans le sérum sanguin de tous les sujets traités avec des composés antioxydants par voie topique ou orale. Les radicaux libres retrouvés aussi bien dans le sérum sanguin que dans la peau (in-vivo) et la ROS induite par l'irradiation des leucocytes avec la lumière ultraviolette (in-vitro) apparaissent significativement moins élevés chez les sujets traités aux antioxydants par voie topique ou orale. D'après les données obtenues il semble possible de conclure que tous les composés utilisés jouent un rôle intéressant comme photoprotecteurs topiques et systémiques grâce à leurs intéressantes propriétés antioxydantes. De plus, le traitement antioxydant semble être une approche thérapeutique prometteuse en ce qu'elle réduit aussi le stress oxydant des personnes touchées par le vieillissement. [source]

Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2009
Cristina W. Nogueira
Abstract Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4 -induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (, -ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

JOURNAL OF APPLIED TOXICOLOGY, Issue 7 2008
V. C. Borges
Abstract The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting , -ALA-D activity (, -aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 µmol kg,1, respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic , -ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated , -ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Parabens, oestrogenicity, underarm cosmetics and breast cancer: a perspective on a hypothesis

JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2003
Philip W. Harvey
Abstract A recent review by Darbre (2003) published in this journal (J. Appi. Toxicol. 23: 89,95) has attracted public and scienti,c interest that requires perspective, particularly on the use of esters of p -hydroxybenzoic acid (parabens) as preservatives in underarm cosmetics. Although parabens are generally regarded as safe, recent reports suggest that they are oestrogenic in a variety of in vitro (including MCF7 and ZR-75-1 human breast cancer cell lines) and in vivo tests for oestrogenicity (uterotrophic assays in both rat and mouse). There are also recent reports of adverse reproductive and developmental outcomes in rodent toxicity studies. Of interest is the lack of activity by the oral route but clear activity by the subcutaneous and topical routes, which is of some relevance to the use of underarm cosmetics. There would seem to be a case now to supplement these emerging toxicity data with longer term regulatory standard tests examining other oestrogenic endpoints and at least to consider these ,ndings in more up-to-date risk assessments speci,c for cosmetic use. Further, there are few data on the use of underarm cosmetics and the risk of breast cancer, and although one recent retrospective interview-based study found no association there is a need for more thorough investigation taking into account the type of chemicals used. Darbre has forwarded a hypothesis and called for further work to establish whether or not the use of underarm cosmetics (particularly containing oestrogenic formulants) contributes to the rising incidence of breast cancer. It would seem prudent to conduct this work because the current database is sparse and the effects of long-term low-level exposures to weakly oestrogenic chemicals on human health, particularly their application to the underarm and the risks of breast cancer, are unknown. The role of oestrogens in breast cancer, however, is undisputed. Copyright © 2003 John Wiley & Sons, Ltd. [source]

Experimental hepatitis A virus infection in guinea pigs

JOURNAL OF MEDICAL VIROLOGY, Issue 4 2001
Britt Hornei
Abstract Although many of the properties of hepatitis A virus (HAV) are known, several aspects of HAV pathogenesis are still not understood, such as the mechanism underlying the hepatotropism or HAV replication in extrahepatic sites. Detailed studies of these aspects were hampered mostly by the lack of accessible animal models, since only nonhuman primates are susceptible to experimental infections. An alternative animal model would also be of interest to assess the primary replication site and for the evaluation of the safety and efficacy of vaccines. A study was undertaken to determine whether HAV can infect guinea pigs and whether they are useful as a model for studying aspects of HAV pathogenesis and for the evaluation of vaccines. HAV variants adapted to primate or guinea pig tissue culture were used to inoculate guinea pigs intraperitoneally and by the oral route. The animals were observed for clinical disease, shedding of HAV in stools, viremia, seroconversion, evidence for liver damage by biochemical liver function tests, virus presence in the liver, development of hepatic histopathological changes, and occurrence of HAV in extrahepatic organs. The animals developed an active, clinically inapparent infection with specific histopathological changes in the liver. Although virus replication occurred, as shown by RT-PCR and isolation of infectious virus from feces and serum, it seems unlikely that guinea pigs are suitable for studying the clinical features of hepatitis A, because the clinical and laboratory parameters remained normal. However, guinea pigs appear useful for studying some aspects of HAV pathogenesis and for testing the safety of vaccines. J. Med. Virol. 64:402,409, 2001. © 2001 Wiley-Liss, Inc. [source]

Randomized controlled trial of oral versus intravenous fluid supplementation on serum bilirubin level during phototherapy of term infants with severe hyperbilirubinaemia

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2002
N-Y Boo
Objective: To compare the rates of decrease in serum bilirubin levels in severely jaundiced healthy term infants given oral or intravenous fluid supplementation during phototherapy. Methods: A randomized controlled study was carried out in the neonatal intensive care unit (NICU) of Hospital Universiti Kebangsaan Malaysia over a 12-month period. Fifty-four healthy term infants with severe hyperbilirubinemia were randomized to receive either solely enteral feeds (n = 27) or both enteral and intravenous (n = 27) fluid during phototherapy. Results: There were no significant differences in the mean birthweight, mean gestational age, ethnic distribution, gender distribution, modes of delivery and types of feeding between the two groups. Similarly, there was no significant difference in the mean indirect serum bilirubin (iSB) level at the time of admission to the NICU between the enteral (359 ± 69 ,mol/L [mean ± SD]) and intravenous group (372 ± 59 ,mol/L; P = 0.4). The mean rates of decrease in iSB during the first 4 h of phototherapy were also not significantly different between the enteral group (10.4 ± 4.9 ,mol/L per h) and intravenous group (11.2 ± 7.4 ,mol/L per h; P = 0.6). There was no significant difference in the proportion of infants requiring exchange transfusion (P = 0.3) nor in the median duration of hospitalization (P = 0.7) between the two groups. No infant developed vomiting or abdominal distension during the study period. Conclusion: Severely jaundiced healthy term infants had similar rates of decrease in iSB levels during the first 4 h of intensive phototherapy, irrespective of whether they received oral or intravenous fluid supplementation. However, using the oral route avoided the need for intravenous cannulae and their attendant complications. [source]

Mechanisms involved in the antinociceptive effect caused by diphenyl diselenide in the formalin test

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2008
Lucielli Savegnago
This study investigated the mechanisms involved in the antinociceptive action induced by diphenyl diselenide ((PhSe)2) in the formalin test. Mice were pre-treated with (PhSe)2 by the oral route (0.1,100 mg kg,1), 30 min before formalin injection. To address some of the mechanisms by which (PhSe)2 inhibits formalin-induced nociception mice were treated with different drugs. The antinociceptive effect of (PhSe)2 was shown in the first and second phases of the formalin test. The antinociceptive effect caused by (PhSe)2 (10 mg kg,1, p.o.) was prevented by intrathecal injection of K+ channel blockers such as apamin and charybdotoxin (small- and large-conductance Ca2+ -activated K+ channel inhibitors, respectively) and tetraethylammonium (TEA, a non-selective voltage-dependent K+ channel inhibitor), but not glib-enclamide (an ATP-sensitive K+ channel inhibitor). The antinociceptive action caused by (PhSe)2 (10 mg kg,1, p.o.) was also blocked by a nitric oxide (NO) synthase inhibitor (N, -nitro- l -arginine, L-NOARG) and the soluble guanylate cyclase inhibitors 1H -[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ) and methylene blue. These results suggest the participation of NO/cyclic GMP/Ca2+ and K+ channel pathways in the antinociceptive effect caused by (PhSe)2. [source]

Reinstatement of Ethanol-Seeking Behavior Following Intravenous Self-Administration in Wistar Rats

ALCOHOLISM, Issue 9 2007
Justin T. Gass
Background: In animal models of alcoholism, subjects are traditionally trained to self-administer ethanol via the oral route. However, ethanol is also self-administered intravenously (IV), a paradigm which offers several advantages over oral self-administration methods, including immediate delivery to the bloodstream, more rapid onset of pharmacological effects, and elimination of the need to utilize tastants or sweeteners to mask the aversive orosensory properties of ethanol. However, no studies to date have examined reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration. Methods: Male Wistar rats were implanted with indwelling jugular vein catheters and trained to self-administer ethanol IV (1% v/v solution, equivalent to 1 mg/kg) in an operant lever-pressing paradigm in twice daily 1 hour sessions. Each IV delivery of ethanol was paired with presentation of a light-tone complex stimulus. After stabilization of response patterns, IV self-administration behavior was subjected to extinction procedures. Next, animals were exposed to the three types of stimuli known to reinstate ethanol-seeking behavior: presentation of ethanol-associated cues, a priming dose of ethanol (0.5 g/kg i.p.), or exposure to stress via administration of the anxiogenic compound yohimbine (2.5 mg/kg i.p.) or its corresponding vehicle. Results: During the maintenance phase of self-administration, animals exhibited significantly more presses on the lever that delivered the ethanol solution than the inactive lever, indicating that IV ethanol functioned as a positive reinforcer. Following extinction, it was found that ethanol-seeking behavior could be reinstated by all three types of stimuli (cues, ethanol priming, and yohimbine). Vehicle injection did not affect responding on either lever. Conclusions: Ethanol serves as a reinforcer when self-administered IV, and following extinction, ethanol-seeking behavior can be reinstated by ethanol-associated cues, ethanol priming, or a pharmacological stressor. Thus, reinstatement of ethanol-seeking behavior in animals with a history of IV ethanol self-administration may be a novel animal model of relapse. [source]

Pharmacokinetics of sulfadimethoxine and ormetoprim in a 5:1 ratio following intraperitoneal and oral administration, in the hybrid striped bass (Morone chrysops × Morone saxitalis)

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2004
R. S. Bakal
Selected pharmacokinetic parameters for sulfadimethoxine and ormetoprim, administered in a 5:1 ratio, via the oral and intraperitoneal (i.p.) routes were determined in the hybrid striped bass (Morone chrysops × Morone saxitalis). Plasma concentrations of both drugs were determined by high-performance liquid chromatography. A first-order one-compartment model adequately described plasma drug disposition. The elimination half-lives for sulfadimethoxine following i.p. and oral administration were 26 and 10.5 h, respectively. The half-lives for ormetoprim administered via i.p. and oral routes were 7.5 and 3.9 h, respectively. Cmax for sulfadimethoxine via the i.p. and oral routes were calculated to be 27.7 (±9.0) ,g/mL at 3.6 h and 3.2 (±1.2) ,g/mL at 1.2 h, respectively. Cmax for ormetoprim via the i.p. route was calculated to be 1.2 (±0.5) ,g/mL at 9.1 h and 1.58 (±0.7) ,g/mL at 5.7 h for the oral route. The oral availability of sulfadimethoxine relative to the i.p. route was 4.6%, while the oral availability of ormetoprim relative to the i.p. route was 78.5%. Due to the nonconstant ratio of these drugs in the plasma of the animal, the actual drug ratio to use for determining minimum inhibitory concentration (MIC) is unclear. Using the ratio of the total amount of each drug that is absorbed as a surrogate for the mean actual ratio may be the best alternative to current methods. Using this ratio as determined in these studies, (2.14:1 sulfadimethoxine:ormetoprim) to determine the MICs the single 50 mg/kg oral dose of the 5:1 combination of sulfadimethoxine and ormetoprim appears to provide plasma concentrations high enough to inhibit the growth of Yersinia ruckeri, Edwardsiella tarda, and Escherichia coli. [source]

Aluminium per se and in the anti-acid drug sucralfate promotes sensitization via the oral route

ALLERGY, Issue 6 2009
R. Brunner
Background:, Aluminium (ALUM) is used as experimental and clinical adjuvant for parenteral vaccine formulation. It is also contained in anti-acid drugs like sucralfate (SUC). These anti-acids have been shown to cause sensitization to food proteins via elevation of the gastric pH. The aim of this study was to assess the oral adjuvant properties of ALUM, alone or contained in SUC, in a BALB/c mouse model. Methods:, Mice were fed SUC plus ovalbumin (OVA) and compared with groups where ALUM or proton pump inhibitors (PPI) were applied as adjuvants. The humoral and cellular immune responses were assessed on antigen-specific antibody and cytokine levels. The in vivo relevance was investigated in skin tests. Results:, The highest OVA-specific immunoglobulin G1 (IgG1) and IgE antibody levels were found in mice fed with OVA/SUC, followed by OVA/ALUM-treated animals, indicating a T helper 2 (Th2) shift in both groups. Antibody levels in other groups revealed lower (OVA/PPI-group) or baseline levels (control groups). Positive skin tests confirmed an allergic response in anti-acid or adjuvant-treated animals. Conclusions:, Our data show for the first time that ALUM acts as a Th2-adjuvant via the oral route. This suggests that orally applied SUC leads to an enhanced risk for food allergy, not only by inhibiting peptic digestion but also by acting as a Th2-adjuvant by its ALUM content. [source]

Effects of sodium benzoate on the complications of 1.

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2004
5% glycine solution using two different intravesical pressures during bladder irrigation
Background:, In this experimental study we researched the effects of sodium benzoate on the complications of 1.5% glycine solution using with two different intravesical pressures during bladder irrigation. Methods:, Thirty-six male adult New Zealand rabbits with body weight ranging from 1500 to 2800 g were used in the experiments. The rabbits were randomly allocated to four groups. In groups 1 and 2, 500 ml of 1.5% gylcine was used as irrigating fluid during 30 min, but only group 2 received 500 mg kg,1 of sodium benzoate treatment by oral route immediately after irrigation. In groups 3 and 4, 500 ml of 1.5% glycine was used as irrigating fluid during 60 min, but only group 4 received the same treatment as group 2. Ammonia, urea, sodium, potassium, hemoglobin, hemotocrit and platelet levels were studied at preirrigation and postirrigation on the 4 h and 24 h. Also electrocardiographic (ECG) changes were monitored at the same time with blood parameters. Results:, At 4 h postirrigation, Na+ levels were decreased significantly in group 1 and non-significantly in group 3 when compared with preirrigation levels. But these levels were not changed in groups 2 and 4. Both at 4 h and 24 h, ammonia and urea levels were significantly increased in groups 1 and 3. Ammonia level was decreased but the urea level was not changed in groups 2 and 4 at the same time points. K+ level was significantly changed only in group 1 at 4 h and 24 h. Hemoglobin and hemotocrit concentrations were decreased both at 4 h and 24 h compared with preirrigation levels in all groups. Also there were ECG changes between the treated and untreated groups. Conclusion:, Sodium benzoate was very effective against the complications of 1.5% glycine during bladder irrigation experimentally. But this needs further investigation, especially for the applicability of this new treatment model in human TURP syndrome. [source]

Therapeutic doses of glucocorticoids: implications for oral medicine

ORAL DISEASES, Issue 5 2006
SK Baid
Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic,pituitary,adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use. [source]

Intravenous cyclophosphamide is the drug of choice for steroid dependent nephrotic syndrome

PEDIATRICS INTERNATIONAL, Issue 1 2003
ZELAL B
AbstractBackground: Steroid dependency is a major problem seen after therapy for idiopathic nephrotic syndrome in childhood. Although there is consensus about the usage of cyclophosphamide (CYC) in frequent relapsers, there is still a controversy concerning its usage in steroid-dependent nephrotic syndrome (SDNS). Methods: In the present study, nineteen children with SDNS were treated with CYC: ten via the intravenous (i.v.) route, and nine via the oral route. Remission was then maintained with prednisolone. Oral CYC therapy consisted of CYC at a dose of 2 mg/kg per day for 12 weeks. Intravenous (i.v.) CYC therapy consisted of CYC 500 mg/m2 per month (with intravenous 3500 cc/m2 per 24 h one-third saline hydration) for 6 months. Results: The cumulative dose of CYC was 168 mg/kg in the oral group and 132 mg/kg in the IV group. Daily oral CYC dose was 1.96~0.31 mg/kg, whereas i.v. CYC dose was 0.73~0.03 mg/kg. Long-term complications and side-effects such as alopecia, infection and hemorrhagic cystitis were not observed in the i.v. CYC treated group. In the long term, the dosage of prednisolone that held remission after CYC, the annualized relapse rates and the subsequent relapse time were significantly better in the i.v. CYC group, and the number of patients in remission for 2 years was significantly higher in the i.v. treated group (P<0.05). Conclusion: In SDNS, i.v. CYC has a long lasting effect with lower annualized relapse rates and longer subsequent relapse time with a lower steroid dosage required to maintain remission than oral CYC. The results of the present study showed the safety of the i.v. route, and it is the preferable treatment in noncompliant patients for its long lasting remission and simple and inexpensive follow up. [source]

Prediction of herb,drug metabolic interactions: a simulation study

PHYTOTHERAPY RESEARCH, Issue 6 2005
Shufeng Zhou
Abstract In vitro and in vivo studies have indicated that the induction or inhibition of cytochrome P450 (CYP) is one of the major mechanisms for some clinically important pharmacokinetic herb,drug interactions. An attempt was made to simulate the effects of herbal preparation with single or multiple CYP-inhibiting constituents on the area of the plasma concentration-time curve (AUC) of coadministered drug that was either a low clearance drug by intravenous (i.v.) injection or a high clearance drug by oral route. Our simulation studies indicated that the expected increase (Rc) in the AUC of the coadministered drug by inhibiting herbal constituent(s) was dependent on the route of administration. For low clearance drug by i.v. injection, Rc was generally determined by inhibition constant (Ki), unbound inhibitor concentration ([I]), hepatic fraction (fh), number of inhibitory herbal constituents (n) and metabolic pathway fraction in hepatic metabolism (fm), while Rc for a high clearance drug by oral route, Rc was determined by Ki, [I], n and fm. By varying these parameters, Rc changed accordingly. It appeared likely to predict a herb,drug metabolic interaction, if the inhibiting herbal constituents could be quantitatively determined. However, many herb- and drug-related factors may cause difficulties with the prediction, and thus in vivo animal and human studies are always necessary. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Bronchoscopy in Japan: A survey by the Japan Society for Respiratory Endoscopy in 2006

RESPIROLOGY, Issue 2 2009
Hiroshi NIWA
ABSTRACT Background and objective: In order to obtain information on the clinical application of bronchoscopy in Japan, the Japan Society for Respiratory Endoscopy (JSRE) conducted a postal survey. Methods: A questionnaire was sent to 526 authorized institutes of the JSRE. The subject was bronchoscopy procedures performed during 2006. Results: The response rate was 71.3%. The total number of bronchoscopies performed was 74 770. Of these, 74 412 were flexible bronchoscopies and 358 were rigid bronchoscopies. At least one JSRE-authorized specialist had worked with 97% of respondents. Eighty-five per cent of respondents performed bronchoscopy under topical anaesthesia for almost all patients. Seventy-five per cent of respondents routinely used the oral route. The reported numbers of diagnostic bronchoscopies was 12 509 for simple bronchoscopy, 25 971 for forceps biopsy, 26 289 for brush biopsy, 25 659 for bronchial washing, 1387 for transbronchial needle aspiration and 6716 for BAL. Three deaths were caused by forceps biopsy (0.012%). The morbidity rates for these diagnostic procedures ranged from 0.14% to 2.5%. The reported numbers of therapeutic bronchoscopies was 476 for tracheobronchial stent, 164 for neodymium (Nd): yttrium-aluminium garnet (YAG) laser photoresection (LPR), 40 for photodynamic therapy, 81 for balloon dilatation, 145 for endobronchial electrocautery, 120 for argon plasma coagulation, 109 for microwave coagulation (MWC), 116 for ethanol injection, 110 for foreign body removal and 89 for bronchial occlusion. Deaths occurred only as a consequence of Nd : YAG LPR (0.61%). The morbidity rates for these therapeutic procedures ranged from 0% to 5%. Conclusions: The preparation for, and practice of, bronchoscopy varied greatly between respondents. Diagnostic bronchoscopy was well tolerated and safe. Therapeutic procedures did not appear to be practised widely or frequently. [source]

Evaluations of toxicity of Turraeanthus africanus (Méliaceae) in mice

ANDROLOGIA, Issue 6 2009
D. Massoma Lembè
Summary Turraeanthus africanus (Meliacaeae) is known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties. However, no extensive safety studies have been conducted on these extracts to date. The aim of this study was to evaluate toxicity of the aqueous extract of Turraeanthus africanus (Meliacaeae) after oral and intraperitoneal administration in mice. The acute toxicity was evaluated after single daily administration of the aqueous extract orally at doses of 0, 5, 10, 15, 20, 30 g kg,1 or by the intraperitoneal route at doses of 0, 3, 6, 9, 12 g kg,1 of raw material. The subacute toxicity was evaluated only by the intraperitoneal route for 6 weeks at doses of 1.5, 3, 6 g kg,1 of raw material. Oral doses up to 30 g kg,1 of the aqueous extract of Turraeanthus africanus (TA) did not produce mortality or significant changes in the general behaviour and gross appearance of internal organs of rats. However, the intraperitoneal administration of the aqueous extract of Turraeanthus africanus caused dose-dependent lethal effects. The acute intraperitoneal toxicity (LD50) of TA extract in mice was 7.2 g kg,1. In subacute toxicity in mice, after the intraperitoneal administration of TA extract for 6 consecutive weeks, the feed consumption was significantly affected at the dose 3 g kg,1 with P < 0.05 and at the dose 6 g kg,1 with P < 0.001 and consequently had significant effect with P < 0.05 in body weight of animals. Level of triglyceride of treated animals lowered at dose 1.5 g kg,1 with P < 0.001 and at dose 3 g kg,1 and 6 g kg,1 with P < 0.05. Total cholesterol level of treated animals lowered at dose 1.5 g kg,1 with P < 0.005 and at dose 3 and 6 g kg,1 with P < 0.001. HDL cholesterol level of treated animals lowered up to dose 6 g kg,1 with P < 0.05 while levels of LDL cholesterol, serum and tissue creatinine of treated animals lowered at dose 3 g kg,1 and dose 6 g kg,1 with P < 0.05. Serum protein level of treated animal enhanced at dose 1.5 g kg,1 and at dose 6 g kg,1 with P < 0.05 while tissue creatinine level of treated animal enhanced with P < 0.001. The histology of liver, kidney and lung of the treated mice indicated morphological change of these organs (data not shown). No significant difference was observed during treatment concerning the haematological parameters. The results suggest that the plant is not toxic through the oral route in mice and that parenteral administration should be avoided. [source]

Comparison of the pharmacokinetics of moxidectin and ivermectin after oral administration to beagle dogs

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2007
Sayer I. Al-Azzam
Abstract This study compares plasma disposition kinetics of ivermectin and moxidectin after oral administration to beagle dogs experimentally infected with the filarial parasite, Brugia pahangi. Sixteen dogs were selected and randomly allocated into two groups of eight dogs each. Animals in each group received either ivermectin or moxidectin by oral route at a dose of 250 µg/kg. Blood samples were collected from 0.5 h up to 56 days post-treatment and the plasma was analysed by high performance liquid chromatography (HPLC). The obtained data were analysed by compartmental and non-compartmental pharmacokinetic techniques. Peak plasma concentrations (Cmax) of 234.0 ± 64.3 ng/ml (mean ± SD) were obtained for moxidectin and 132.6 ± 43.0 ng/ml for ivermectin. The terminal elimination half-life was significantly (p<0.01) longer in the moxidectin treated group (621.3 ± 149.3 h) than for ivermectin treated group (80.3 ± 29.8 h). A significantly (p< 0.01) larger Vss/F was obtained for moxidectin (19.21 ± 3.61 l/kg) compared with ivermectin (5.35 ± 1.29 l/kg). The mean estimates of CL/F of moxidectin and ivermectin were 0.0220 ± 0.00381 and 0.0498 ± 0.0179 l/h/kg, respectively. The comparative plasma disposition kinetics of ivermectin and moxidectin in dogs is reported for the first time. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Stereoselective pharmacokinetic analysis of tramadol and its main phase I metabolites in healthy subjects after intravenous and oral administration of racemic tramadol

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2007
Emilio García Quetglas
Abstract The kinetics of tramadol enantiomers are stereoselective when doses of the racemic drug are given orally. To document whether the route of administration determines the stereoselective kinetics of tramadol enantiomers, healthy volunteers received 100 mg oral or intravenous doses of racemic tramadol, and serial blood samples were obtained to assay tramadol enantiomers and their main phase I metabolites, O -demethyltramadol and N -demethyltramadol. To assess accurately the involvement of their metabolites in the pharmacokinetics of tramadol, it is essential to determine the rate and extent of the formation of the enantiomers of these metabolites. A simultaneous pharmacokinetic model describing the plasma concentration-curves of the generated metabolites and the parent compounds after intravenous and oral drug administration is developed and presented. Tramadol and O -demethyltramadol were the major compounds detected in plasma after intravenous administration. Nevertheless, the N -demethylation of tramadol showed a significant increase when the oral route was used. After both oral and intravenous doses, the kinetics of the tramadol enantiomers were stereoselective. The AUC for (R )-(+)-tramadol was greater than the AUC for (S)-(,)-tramadol. The formation of N -demethyltramadol also was enantioselective after oral administration of racemic tramadol, with a greater AUC for (R)-(+)- N -demethyltramadol than for (S)-(,)- N -demethyltramadol. In the opposite form, (S)-(,)- O -demethyltramadol was formed faster than (R)-(+)- O -demethyltramadol. The metabolism of tramadol was also route-dependent with a different enantiomeric ratio for tramadol and its main phase I metabolites after intravenous and oral administration. The disposition of N -demethyltramadol was concentration-dependent. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2002
Andries Pelser
Abstract The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, Cmax, tmax) following intranasal, oral and intravenous administrations. Subjects (six male Sprague,Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25±1°C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid,liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (Cmax) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve Cmax for the intranasal route (tmax=0.5 h) was faster than for the oral route (tmax=1.5 h), but no statistically significant differences between the Cmax values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Effectiveness and cost of bisphosphonate therapy in tumor bone disease

CANCER, Issue S3 2003
Jean-Jacques Body M.D., Ph.D.
Abstract BACKGROUND Tumor-induced osteolysis due to breast carcinoma and myeloma is responsible for a considerable morbidity that severely impairs patients'quality of life. Osteoclast-mediated bone resorption is reported to be increased markedly in patients with tumor bone disease and can be inhibited by bisphosphonate therapy. METHODS The incidence of skeletal complications and the effectiveness of bisphosphonate therapy in patients with breast carcinoma metastatic to bone or in those with myeloma were derived from large-scale, long-term, placebo-controlled trials with clodronate or pamidronate. To the authors' knowledge, there are few studies published to date evaluating the cost-effectiveness of bisphosphonate therapy, and the majority that do exist often are based on models and are applicable only to a particular health care system. RESULTS From the placebo groups of the above-mentioned trials, one can estimate that approximately 25,40% of the patients with breast carcinoma metastatic to bone will require radiotherapy for bone pain and approximately 17,50% will sustain incident vertebral fractures yearly. The incidence of complications is reported to be lower in myeloma patients. The prolonged administration of bisphosphonates reportedly can reduce the frequency of skeletal-related events by approximately 25,50%. Maximal efficacy appears to have been achieved with the current therapeutic schemes based on monthly intravenous infusions. Beneficial effects appear to be obtained more readily using the intravenous route rather than the oral route. The costs of bisphosphonate therapy appear to be higher than the cost savings from the prevention of skeletal-related events. The costs per quality of life-adjusted year have been estimated to be > $100,000, but more research is needed. Limited data suggest that zoledronic acid will not reduce treatment costs but the short infusion time will lead to substantial time savings for patients and for outpatient oncology facilities. CONCLUSIONS As is the case for many agents used in oncology, bisphosphonates remain a relatively expensive therapy. More studies are needed to evaluate their cost-effectiveness ratio correctly. A ceiling effect has been reached with current therapeutic schemes and tailoring therapy to the individual patient needs to be evaluated correctly to increase therapeutic effectiveness and improve quality of life further without increasing treatment costs. Cancer 2003;97(3 Suppl):859,65. © 2003 American Cancer Society. DOI 10.1002/cncr.11139 [source]

Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayers

CELLULAR MICROBIOLOGY, Issue 2 2008
Aurélie Couesnon
Summary Botulism is mainly acquired by the oral route, and botulinum neurotoxin (BoNT) escapes the gastrointestinal tract by crossing the digestive epithelial barrier prior to gaining access to the nerve endings. Here, we show that biologically active BoNT/A crosses intestinal cell monolayers via a receptor-mediated transcytosis, including a transport inhibition at 4°C and a passage at 37°C in a saturable manner within 30,60 min. BoNT/A passage rate was about 10-fold more efficient through the intestinal crypt cell line m-ICcl2, than through the carcinoma Caco-2 or T84 cells, and was not increased when BoNT/A was associated with the non-toxic proteins (botulinum complex). Like for neuronal cells, BoNT/A binding to intestinal cells was mediated by the half C-terminal domain as tested by fluorescence-activated cytometry and by transcytosis competition assay. A ,double receptor model' has been proposed in which BoNT/A interacts with gangliosides of GD1b and GT1b series as well as SV2 protein. Gangliosides of GD1b and GT1b series and recombinant intravesicular SV2-C domain partially impaired BoNT/A transcytosis, suggesting a putative role of gangliosides and SV2 or a related protein in BoNT/A transcytosis through Caco-2 and m-ICcl2 cells. [source]

Plant non-specific lipid transfer proteins as food and pollen allergens

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2004
G. Salcedo
Summary Several members of the plant non-specific lipid transfer protein (LTP) family have been identified as relevant allergens in foods and pollens. These allergens are highly resistant to both heat treatment and proteolytic digestion. These characteristics have been related with the induction of severe systemic reactions in many patients, and with the possibility of being primary sensitizers by the oral route. A specific geographical distribution pattern of sensitization to LTP allergens has been uncovered. This allergen family is particularly important in the Mediterranean area, but shows a very limited incidence in Central and Northern Europe. The potential role in the plant, as well as the biochemical and allergenic properties of the LTP family, are reviewed here. [source]

Larvae and early post-larvae of Penaeus monodon (Fabricius) experimentally infected with white spot syndrome virus (WSSV) show no significant mortality

JOURNAL OF FISH DISEASES, Issue 7 2003
K Yoganandhan
Abstract The pathogenicity of white spot syndrome virus (WSSV) was tested with different developmental stages of Penaeus monodon, i.e. nauplius, protozoeae, mysis, early post-larvae (PL1-10), late post-larvae (PL11-20) and juveniles. WSSV challenge was done by immersion and oral routes. No disease occurred in the larvae and early post-larvae but they were positive for WSSV by nested polymerase chain reaction (PCR) assay. Significant mortality was observed in late post-larvae and juveniles and both single and nested PCR assays gave positive results with these samples. The results demonstrated that WSSV virulence in P. monodon increases with advancing stages of development and that WSSV infection does not result in disease for larvae and post-larvae younger than PL10. [source]

Alternate delivery route for amifostine as a radio-/chemo-protecting agent

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2008
Natalie P. Praetorius
Amifostine (ethiofos, WR-2721) is an organic thiophosphate prodrug that serves as an antineoplastic adjunct and cytoprotective agent useful in cancer chemotherapy and radiotherapy. The selective protection of certain tissues of the body is believed to be due to higher alkaline phosphatase activity, higher pH and vascular permeation of normal tissues. Amifostine is conventionally administered intravenously before chemotherapy or radiotherapy. It is approved by the Food and Drug Administration (FDA) to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. It was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer although this indication was withdrawn in 2005. Amifostine is also FDA approved for patients with head and neck cancer to reduce the incidence of moderate to severe xerostomia in patients who are undergoing postoperative radiation treatment where the radiation port includes a substantial portion of the parotid glands. The potential of amifostine as a cytoprotective agent is unlikely to be fully realized if the method of administration is restricted to intravenous administration. Attempts have been made to develop non-invasive methods of delivery such as transdermal patches, pulmonary inhalers, and oral sustained-release microspheres. It is the goal of this article to explore non-intravenous routes of administration associated with better efficacy of the drug. This review will primarily focus on the variety of more recently studied (2002 and later) alternative modes for amifostine administration, including subcutaneous, intrarectal and oral routes. [source]

Pharmacokinetic-pharmacodynamic integration of moxifloxacin in rabbits after intravenous, intramuscular and oral administration

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2005
E. FERNÁNDEZ-VARÓN
The pharmacokinetics of moxifloxacin was studied following intravenous (i.v.), intramuscular (i.m.) and oral dose of 5 mg/kg to healthy white New Zealand rabbits (n = 6). Moxifloxacin concentrations were determined by HPLC assay with fluorescence detection. The moxifloxacin plasma concentration vs. time data after i.v. administration could best be described by a two-compartment open model. The disposition of i.m. and orally administered moxifloxacin was best described by a one-compartment model. The plasma moxifloxacin clearance (Cl) for the i.v route was (mean ± SD) 0.80 ± 0.02 L/h·kg. The steady-state volume of distribution (Vss) was 1.95 ± 0.18 L/kg. The terminal half-life (t1/2,z) was (mean ± SD) 1.84 ± 0.12, 2.09 ± 0.05 and 2.15 ± 0.07 h after i.v., i.m. and oral, respectively. Minimal inhibitory concentration (MIC) assays of moxifloxacin against different strains of S. aureus were performed in order to compute pharmacodynamic surrogate markers. From these data, it is concluded that a 5 mg/kg dose moxifloxacin would be effective by i.m. and oral routes in rabbits against bacterial isolates with MIC , 0.06 ,g/mL and possibly for MIC , 0.12 ,g/mL, but in the latter case a higher dose would be required. [source]

Pharmacokinetics of sulfadimethoxine and ormetoprim in a 5:1 ratio following intraperitoneal and oral administration, in the hybrid striped bass (Morone chrysops × Morone saxitalis)