Pharmacokinetic drug interactions between triamterene and ranitidine in humans: alterations in renal and hepatic clearances and gastrointestinal absorption.
Ranitidine reduces the renal tubular secretion of the organic cations procainamide and N-acetylprocainamide in humans through competition for transport via the organic cation transport system. Ranitidine is thought to spare phase I hepatic metabolism mediated by cytochrome P-450, unlike its counterpart H2-receptor antagonist cimetidine. The aim of the present study was to determine, in eight human subjects, the effect of ranitidine on the disposition of the potassium-sparing diuretic triamterene, which undergoes renal tubular secretion, hepatic hydroxylation and subsequent sulphate conjugation to a pharmacologically active metabolite. Multiple blood and urine samples were collected throughout a dosing interval after chronic administration of triamterene alone, ranitidine alone or the two in combination. Ranitidine significantly (P less than .05) reduced the renal clearances of triamterene (51%) and p-hydroxytriamterene sulphate conjugate (47%), the clearance by hydroxylation of triamterene (30%) and the apparent absorption of triamterene (52%). In turn, triamterene reduced the renal clearance of ranitidine (14%). The interaction resulted in a small attenuation of the pharmacodynamic response to triamterene. These results necessitate consideration of the underlying mechanisms of the interactions and fall outside of our present understanding of the renal clearance of sulphate conjugates and the metabolic inhibitory effects of ranitidine. Competition for translocation across membranes is postulated as a common mechanism for the observed renal and hepatic interactions.
Muirhead
M
M
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Bochner
F
F
Somogyi
A
A
D000328:Adult; D004347:Drug Interactions; D004573:Electrolytes / Q000652:urine; D006801:Humans; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011899:Ranitidine / Q000493:pharmacokinetics* / Q000494:pharmacology; D014223:Triamterene / Q000493:pharmacokinetics* / Q000494:pharmacology
D004573:Electrolytes; D011899:Ranitidine; D014223:Triamterene