Mechanisms of nonlinear pharmacokinetics of sulfadimethoxine in cocks.

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Abstract
Pharmacokinetics of sulfadimethoxine (SDM) after 3 intravenous doses (10, 30 and 90 mg/kg) was studied in 5 cocks (8 months old). The plasma concentration curves after 30 and 90 mg/kg doses showed a nonlinear pharmacokinetics, in which the initial elimination curves were declined slower with increasing doses. The corrected values of the area under the plasma concentration versus time curves (AUC) which were obtained by divided AUC of SDM by the ratio of 30 and 90 mg/kg doses to 10 mg/kg dose, increased dose-dependently. SDM, N4-acetyl of SDM (Ac-SDM) and an unknown metabolite of SDM (UK-metabolite) were found in the excreta. The excretion of SDM and Ac-SDM was decreased with time, but the excretion of UK-metabolite was apparently nonlinear excretory kinetics after 30 and 90 mg/kg doses. These results may suggest that the saturation of elimination of UK-metabolite is a possible causative prosses of the nonlinear pharmacokinetics of SDM in cocks. The UK-metabolite was suggested to be a new metabolite because of resistance to hydrolysis by .beta.-glucuronidase or 2N HCL.