Cimetidine and procainamide secretion by proximal tubules in vitro.
Previous studies have shown that organic bases, including some drugs, are secreted by renal proximal tubules. The present studies examined the transport of the organic bases cimetidine and procainamide by rabbit proximal straight tubules perfused in vitro. Both drugs were secreted into the tubule lumen. [3H]cimetidine secretion was reduced by quinidine, procainamide, and N-acetylprocainamide. Previous studies showed that cimetidine secretion was reduced by other organic bases. Hypothermia and ouabain inhibited [3H]procainamide secretion as was shown previously for cimetidine secretion. [3H]procainamide secretion was also reduced by quinidine, cimetidine, procainamide, and N-acetylprocainamide but not by probenecid. High concentrations of cimetidine (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. The results suggest that both cimetidine and procainamide are secreted into the lumen of proximal straight tubules predominately by an organic base transport mechanism. These studies raise the possibility that some of these drugs might compete for a common secretory mechanism in renal tubules and reduce the elimination of each other.
D000042:Absorption; D000120:Acecainide / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011342:Procainamide / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits
D006146:Guanidines; D002245:Carbon Dioxide; D010042:Ouabain; D002927:Cimetidine; D000120:Acecainide; D011802:Quinidine; D011342:Procainamide; D011339:Probenecid