Effect of tolbutamide treatment on the pharmacokinetics of intravenously administered sulphamethoxazole in rabbits.

Fifteen days of tolbutamide treatment significantly decreased the elimination half life (t1/2), area under the curve (AUC0----infinity) and increased the clearance of sulphamethoxazole (SMZ) in rabbits. No significant difference was observed in the volume of distribution. The percentage of plasma protein binding to SMZ was not altered, while N-acetyltransferase activity in liver and kidney was significantly increased after tolbutamide therapy. The changes observed in the pharmacokinetic parameters of SMZ after tolbutamide treatment is due to the induction of liver N-acetyltransferase activity.