Effects of treatment of cimetidine (CMT) on pharmacokinetic behaviors of chlopropamide (CPA), an oral hypoglycemic agent, were investigated in rabbits with the standard renal clearance method. The renal clearance ratio and the renal tubular secretion volume of CPA were found to be markedly decreased by the treatment of CMT. Furthermore, the results of experiments using renal cortical slices demonstrated that CMT of the cationic drug decreased the accumlation of CPA. Inhibition of uptake by 2, 4-dinitrophenol indicated an energy dependence. Probenecid, a competitor for the anion transport mechanism, moderately inhibited CPA uptake.These observations indicate that the treatment of CMT may depress the renal excretion of CPA by inhibiting the tubular secretion.
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