Bioavailability and Disposition Kinetics of Amoxicillin in Normal and Febrile Rabbits

Objective: The study was planed to see bioavailability and disposition kinetics of amoxicillin in adult rabbits (irrespective of sex) under healthy and induced febrile conditions. Design: Comparative Place and duration of study: Study was conducted at the department of pharmacology, University of Veterinary and Animal Sciences, Lahore from January 2003 to July 2003. Methodology: Initially all rabbits were weighed and their packed cell volume (PCV) and other biochemical parameters were observed in normal conditions. Bioavailability and disposition kinetics of amoxicillin (10mg \ Kg body weight) were studied in all normal rabbits following oral and intravenous route of drug administration. A wash out period of 10 days was given in between the two trials. Fever was produced by injecting the E. Coli suspension (prepared in sterilized water) in the marginal ear vein of rabbits at a dosage rate of 0.01 ml per Kg body weight. Blood samples were collected from the rabbits suffering from fever to determine packed cell volume and biochemical parameters. Treated rabbits were administered amoxicillin orally and intravenously (10 mg /Kg body weight). Rectal temperature and behavioral changes were recorded and samples were drawn at prescribed time intervals. Amoxicillin was assessed in plasma by using microbiological assay method. Plasma concentration was analyzed using non compartmental method. Results: A non significant difference was found in biochemical parameters and body weight was found except total lipids. There was significant decrease in (P < 0.01) packed cell volume and plasma concentration of amoxicillin of the febrile rabbits. A statistically significant (P > 0.05) increase in the total lipids was observed in febrile rabbits. The plasma drug concentration of orally administered amoxicillin was significantly lower (p< 0.01) in febrile rabbits. Where as no difference was observed in the intravenous administration of amoxicillin in normal and febrile rabbits. Clearance of the drug was significantly lower in the febrile group. Endotoxin induced fever in rabbits on the biochemical and pharmacokinetic parameters of amoxicillin revealed that in rabbits during Endotoxin induced fever, packed cell volume, total lipids and plasma concentration of amoxicillin decreases significantly (p<0.01 ). The plasma drug concentration of orally administered amoxicillin was significantly lower (P<0.01) in febrile rabbits. The lower plasma drug levels resulted to a smaller area under curve, a larger volume of distribution and a higher clearance value in febrile rabbits. Where as not much difference was observed in the intravenous administration of amoxicillin in normal and febrile rabbits. Clearance of the drug was significantly lower in febrile group placation Conclusion: This study in rabbits indicates the need of modification of dosage regimen under experimentally induced febrile state and warrant clinical evaluation /application. Key Word: Amoxicillin, Febrile