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Phenobarbital minimally alters plasma concentrations of losartan and its active metabolite E‐3174
Author(s) -
Goldberg Michael R.,
Lo Man Wai,
Deutsch Paul J.,
Wilson Susan E.,
McWilliams Edward J.,
McCrea Jacqueline B.
Publication year - 1996
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 - 10.1016/s0009-9236(96)80004-x
Subject(s) - losartan , phenobarbital , metabolite , endocrinology , active metabolite , medicine , chemistry , angiotensin ii , pharmacokinetics , plasma renin activity , placebo , cytochrome p450 , pharmacology , renin–angiotensin system , metabolism , receptor , blood pressure , alternative medicine , pathology
Losartan, a selective angiotensin II (AT 1 ) receptor antagonist for hypertension, is metabolized to an active carboxylic acid metabolite, E‐3174, which has a longer half‐life. To investigate the effects of induction of cytochrome P450 on the metabolism of losartan, we evaluated the effects of phenobarbital on the plasma profiles of losartan and E‐3174 in 15 healthy male subjects. Ten subjects received a single 100 mg oral dose of losartan before and during phenobarbital administration (100 mg/day for 16 days), and five subjects received losartan before and during placebo. Urinary excretion of 6‐β‐hydroxycortisol (relative to 17‐hydroxycorticosteroids) was measured as an endogenous marker of cytochrome P450 induction. The geometric mean area under the plasma concentration‐time curve ratios (with/without phenobarbital and 90% confidence intervals) for losartan and its metabolite (E‐3174) were 0.795 (0.723, 0.875) and 0.799 (0.778, 0.820), respectively, indicating that phenobarbital treatment significantly but to a clinically minor extent reduced plasma concentrations of losartan and E‐3174 ( p < 0.01). Half‐life values of losartan and E‐3174 were unchanged. The ratio of 6‐β‐hydroxycortisol to 17‐hydroxycorticosteroids doubled in the phenobarbital group ( p < 0.001) and did not change appreciably in the placebo group. Clinical Pharmacology & Therapeutics (1996) 59 , 268–274; doi: