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Effect of cimetidine on renal and hepatic drug elimination: Studies with triamterene
Author(s) -
Muirhead Murray R,
Somogyi Andrew A,
Rolan Paul E,
Bochner Felix
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.197
Subject(s) - cimetidine , triamterene , pharmacokinetics , pharmacology , drug interaction , chemistry , urine , drug , dosing , medicine , biochemistry , hydrochlorothiazide , blood pressure
A chronic‐dosing pharmacokinetic study was carried out in six healthy subjects to examine the potential for Cimetidine to reduce the CL R and CL H of triamterene. Blood and urine samples were collected frequently for 24 hours after dosing with triamterene alone (100 mg/day) for 4 days and concomitant Cimetidine (400 mg twice daily) for an additional 4 days. Cimetidine significantly reduced the clearance of triamterene by hydroxylation by 32% (P < 0.016) and the CL R of triamterene by 28% (P < 0.063), with no change in its protein binding. The CL R of the active sulfate conjugate of triamterene was not altered by Cimetidine. There was a reduced recovery of triamterene and its metabolites in urine after Cimetidine, suggesting a decreased absorption. These results are consistent with Cimetidine inhibiting cytochrome P‐450 enzymes in the liver and also competing with triamterene for renal tubular secretion. Despite the pharmacokinetic interaction, Cimetidine caused minimal alteration to the natriuretic and antikaliuretic effects of triamterene. Clinical Pharmacology and Therapeutics (1986) 40, 400–407; doi: 10.1038/clpt.1986.197