Pharmacokinetic behavior of chlorpropamide and sulfadimethoxine in alloxan diabetic rabbits.

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Abstract
Pharmacokinetic behavior of chlorpropamide (CPA) and sulfadimethoxine (SDM) following i.v. administration were studied in rabbits under normal and alloxan diabetic condition. Plasma concentration of both drugs in the .beta. phase in diabetic rabbits sustained a higher level than those under normal condition. The abnormal pattern of the concentration-time curve of SDM recovered to the normal pattern by the 5-day insulin tratement, but CPA was not the case. Renal clearance of CPA, SDM and N4-acetylsulfadimethoxine (N4-AcSDM) were decreased under diabetic condition. The decreased renal clearances of CPA and N4-AcSDM were subjected to the blockade of proximal tubular secretion of both drugs and to the increased renal tubular reabsorption due to urinary acidification under diabetic condition. The decreased renal clearance of SDM was subjected to the increased renal tubular reabsorption alone. Plasma protein binding and distribution into red blood cells of the drugs were also studied under normal and diabetic conditions.

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