Pharmacodisposition of thiamphenicol in rabbits

Abstract

The pharmacokinetic parameters of thiamphenicol (TAP) were studied in New Zealand white rabbits. Five rabbits were each given thiamphenicol as a single 30 mg/kg of body weight dosage by intravenous (i.v.), intramuscular (i.m.) and oral routes. Serum antibacterial concentrations were determined for 72 h after dosing. Compartmental modeling of the i.v. administration indicated that a 2-compartment open model best described the disposition of thiamphenicol in rabbits. Serum thiamphenicol concentrations after i.m. and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for i.v., i.m. and oral routes of administration were 1.39, 2.45, and 1.44 h, respectively. The half-life of absorption for oral dosing was 1.2 times the half-life of absorption after i.m. dosing (0.49 h vs 0.40 h). The calculated time to maximal serum concentration was 1.25 h after i.m. dosing and 1.17 h after oral administration. The calculated serum concentrations at these times were 80.4 and 69.8 micrograms/ml, respectively. Mean residence time's were 1.89 h for i.v. injection, 2.78 h for i.m. dosing and 4.11 h for oral administration. Thiamphenicol was widely distributed in the rabbit as suggested by the volume of distribution value at steady state of 1.47 l/kg calculated from the i.v. study. Bioavailability was 101.4% after i.m. dosing and 64.2% for oral absorption.