Kinetic studies on the competition between famotidine and cimetidine in rats. Evidence of multiple renal secretory systems for organic cations

Abstract

The H2-receptor antagonists famotidine and cimetidine are both basic drugs that are predominantly eliminated by the kidneys. Cimetidine has been shown to inhibit the renal secretion of tetraethyl-ammonium bromide (TEAB) but not p-aminohippuric acid (PAH), suggesting that cimetidine is secreted by an organic cation transport system [Weiner and Roth: J. Pharmacol. Exp. Ther. 216: 516 (1981)]. The present study shows that famotidine behaves like cimetidine in that it also inhibits TEAB but not PAH excretion. Where a high concentration of cimetidine in plasma has an inhibitory effect on the renal excretion of famotidine, the reverse is not true, i.e. high plasma levels of famotidine have no effect on the excretion of cimetidine. Further evidence that additional transport systems are involved in the renal tubular secretion of cimetidine is as follows. Quinine, a potent competitor of the organic cation transport system, inhibits the secretory component of famotidine renal clearance but not that of cimetidine. Probenecid, a classic competitor for the organic anion transport system, inhibits the renal excretion of cimetidine but not famotidine. However, the effect of probenecid is minor and not sufficient to account for other components of cimetidine secretion not affected by famotidine and quinine.