Kinetic disposition, systemic bioavailability, tissue levels and acetylation of some sulphonamides in goats

Abstract

Sulphamethoxazole, sulphadimethyloxazole and sulphadimethoxine were once administered in goats via oral and i.v. route (100 mg/kg b.wt.) for determination of plasma and urine concentrations of the unchanged sulphonamides and their acetylated derivatives, kinetic behavior, systemic bioavailability, tissue levels and acetylation. The highest plasma concentrations of sulphamethoxazole, sulphadimethyloxazole and sulphadimethoxine were reached after 0.64, 1.31 and 0.46 hr following oral administration, with an absorption half-life of 0.84, 1.31 and 0.38 hr and an elimination half-life of 3.51, 5.01 and 5.55 hr, respectively. Following a single i.v. injection, the kinetic disposition of sulphamethoxazole and sulphadimethoxine followed a one-compartmental model with an elimination half-life of 1.48 and 1.76 hr and a total body clearance-time curve of sulphadimethyloxazole, after a single i.v. injection, could be described by a two-compartmental open model with an elimination half-life of 3.27 hr, a volume of distribution of 248.07 ml/kg and a total body clearance of 0.82 ml/kg/min. The systemic bioavailability was 19.95, 11.37 and 23.27% after oral administration of sulphamethoxazole, sulphadimethyloxazole and sulphadimethoxine, respectively. The percentages of serum protein binding of sulphamethoxazole, sulphadimethyloxazole and sulphadimethoxine were determined in most of the body tissues, collected 4 hr after i.v. injection. The highest concentration was found in kidney and liver. On the other hand, sulphamethoxazole, sulphadimethyloxazole and sulphadimethoxine were N4-acetylated in the body tissues to a higher extent than that in plasma. Acetylation was highest in rumen and skeletal muscle.