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Pharmacokinetic behavior of sulfamethoxazole in alloxan diabetic rabbits.

Pharmacokinetic behaviors of sulfamethoxazole (SMX) and its main metabolite, N4-acetyl-sulfamethoxazole (N4-AcSMX) in rabbits were studied under normal and diabetic condition following intravenous administration of SMX. The pharmacokinetic parameters were calculated employing a two compartment model. Under diabetic condition, the elimination rate constant of SMX from plasma showed a marked decrease. Renal excretion rate constants of SMX and N4-AcSMX also decreased under diabetic condition. Distribution of SMX to the tissue compartment increased in diabetic condition but that in the central compartment remained at the same value of normal condition. Changes in parameters under diabetic condition showed a recovering trend by insulin treatment. Plasma Protein binding of SMX and N4-AcSMX were enhanced under diabetic condition. The increase in protein binding was subjected to an increase in the concentration of albumin under diabetic condition. Insulin treatment caused a slight recover of the binding to the values of nornal condition. Thus, it was concluded that the decrease in renal excretion rate constant of SMX and the increase in plasma protein binding of SMX and N4-AcSMX are attributable to a decrease in elimination rate of SMX from plasma. It was also suggested that the decrease in renal excretion of SMX and N4-AcSMX might be caused by changes of the physiological factors such as blood glucose and acetone bodies.