Cimetidine and procainamide secretion by proximal tubules in vitro

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Abstract
Organic bases, including some drugs, are secreted by renal proximal tubules. The transport of the organic bases, cimetidine and procainamide, by rabbit proximal straight tubules perfused in vitro was studied. Both drugs were secreted into the tubule lumen. [3H]cimetidine secretion was reduced by quinidine, procainamide and N-acetylprocainamide. Cimetidine secretion was reduced by other organic bases. Hypothermia and ouabain inhibited [3H]procainamide and cimetidine secretion. [3H]procainamide secretion was also reduced by quinidine, cimetidine, procainamide and N-acetylprocainamide but not by probenecid. High cimetidine concentrations (10-3 M) had no effect on the rates of fluid or total CO2 absorption. When analyzed in terms of Michaelis-Menten kinetics, the effect of cimetidine on procainamide secretion and procainamide on cimetidine secretion was consistent with competitive inhibition. Evidently, both cimetidine and procainamide are secreted into the lumen of proximal straight tubules predominately by an organic base transport mechanism. Some of these drugs might compete for a common secretory mechanism in renal tubules and reduce the elimination of each other.

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