Cimetidine secretion by rabbit renal tubules in vitro
McKinney, T.D.; Myers, P.; Speeg, K.V.
American Journal of Physiology 241(1): F69-F76
1981
ISSN/ISBN: 0002-9513 PMID: 7246776 Document Number: 178870
Cimetidine [N'-cyano-N-methyl-N'{2-[(5-methylimidazol-4-yl)methylthio]ethyl} guanidine] a drug in widespread use in the treatment of peptic ulcer disease in man, is eliminated primarily via urinary excretion. Cimetidine transport was examined in rabbit proximal straight tubules perfused in vitro. [3H]Cimetidine in the bath was actively secreted into the tubule lumen. There was a curvilinear relationship between the rate of cimetidine secretion and the concentration of bath cimetidine. Cimetidine secretion was inhibited by hypothermia and ouabain. Quinine, tolazoline, probenecid, phloridzin, creatinine, p-aminohippurate and cimetidine sulfoxide inhibited cimetidine secretion in a dose-related manner. At low cimetidine concentrations lumen-to-bath transport rates were only 11-18% of bath-to-lumen secretory rates. High performance liquid chromatographic analysis of collected tubular fluid showed a predominance of cimetidine and a small amount of cimetidine sulfoxide in ratios similar to those of the bath. Cimetidine is actively secreted into the lumen of rabbit proximal straight tubules in vitro. Secretion probalby occurs via the organic base and to a lesser extent the acid transport systems.