Tubular transport and metabolism of cimetidine in chicken kidneys.
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, two 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 ot 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.
D000818:Animals; D001692:Biological Transport; D002250:Carbon Radioisotopes; D002645:Chickens; D002794:Choline / Q000494:pharmacology; D002927:Cimetidine / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D011168:Portal System; D011342:Procainamide / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D013831:Thiamine / Q000494:pharmacology
D002250:Carbon Radioisotopes; D006146:Guanidines; D002927:Cimetidine; D011899:Ranitidine; D011342:Procainamide; D002794:Choline; D013831:Thiamine