Pharmacokinetics, intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit model

Abstract

This study investigated the disposition kinetics and plasma availability of ceftazidime in rabbits after single intravenous (i.v.) and intramuscular (i.m.) injections of 50 mg kg-1 b.wt. Tissue residue profiles were studied after repeated intramuscular injections of 50 mg kg-1 b. wt, twice daily for five consecutive days. A microbiological assay with Bacillus subtilis as the test organism was used to measure its concentrations in plasma and tissues. The plasma concentration-vs-time curves were best described by a two compartment open model. The decline in plasma drug concentration was biexponential with half-lives of 0.258 h for t1/2 alpha, 2.22 h for t1/2 beta, for distribution and elimination phases, respectively, following i.v. injection. After intramuscular injection of ceftazidime at the same dose, it was detected in plasma at 5 min and reached its minimum level 12 h post-injection. The peak plasma concentration (Cmax) 66.3 micrograms.ml-1 was attained at 0.779 h (Tmax). The elimination half-life (T1/2el,) was 2.12 h, the mean residence time (MRT) was 3.06 h and the systemic bioavailability was 96.6%. In vitro protein binding percent of ceftazidime in rabbit's plasma was ranged from 13.3 to 21.6%. The limit of quantification (LOQ) for the assay was 0.01 microgram.ml-1 in plasma and tissues. The tissue level concentrations were highest in the kidneys, and decreased in the following order: liver > heart > muscles and plasma. No ceftazidime residues were detected in tissues and plasma after 72 h. It is concluded that tissue kinetics is an important tool in predicting and controlling drug residues in edible tissues of food producing animal.