Tubular transport and metabolism of cimetidine in chicken kidneys
Rennick, B.; Ziemniak, J.; Smith, I.; Taylor, M.; Acara, M.
Journal of Pharmacology and Experimental Therapeutics 228(2): 387-392
1984
ISSN/ISBN: 0022-3565 PMID: 6319677 Document Number: 238219
Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [14C]CIM with decreasing potency: CIM; ranitidine; thiamine; procainamide; guanidine; and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]tetraethylammonium. During CIM infusion, 2 renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did not inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion.