The Effect of Cimetidine on Renal Excretion of Chlorpropamide in Rabbits. (I).

Abstract

Effects of co-administration of cimetidine(CMT) on pharmacokinetic behaviors of chlorpropamide(CPA),an oral hypoglycemic agent,after intravenous injection,were investigated in rabbits.The co-administration of CMT enhanced the plasma concentration of CPA,and reduced the amount of cumulative urinary excretion of CPA after intravenous bolus injection.Furthermore,the co-administration of CMT was found to decrease the renal clearance of CPA significantly,but to have no effect on its extrarenal clearance.These clearly indicate that the interaction of CPA with CMT is generated during renal excretion.For the purpose of elucidating the cause,effects of CMT on plasma protein binding of CPA,glomerular filtration rate (GFR),renal tubular secretion of PSP,and urinary pH were investigated.Plasma protein binding of CPA,GFR,and urinary pH were unchanged with and without CMT.But urinary excretion of PSP was decreased by co-administration of CMT.These observations suggest that the co-administration of CMT may depress the renal excretion of CPA by inhibiting the tubular secretion.