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Differential effect of isoniazid on triazolam oxidation and oxazepam conjugation.
Author(s) -
Ochs HR,
Greenblatt DJ,
Knuchel M
Publication year - 1983
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1983.tb02256.x
Subject(s) - triazolam , oxazepam , chemistry , pharmacology , isoniazid , pharmacokinetics , hypnotic , medicine , benzodiazepine , biochemistry , tuberculosis , receptor , pathology
Healthy volunteers received a single dose of triazolam (0.5 mg) or oxazepam (30 mg) on two occasions, once in the control state and again during coadministration of isoniazid (INH) base, 180 mg day. INH coadministration prolonged triazolam half‐life (3.3 vs 2.5 h, P less than 0.05) and increased total area under the curve (38.6 vs 26.5 ng ml‐ 1 h, P less than 0.01) consistent with a reduction of apparent oral clearance (3.9 vs 6.8 ml min‐1 kg‐1, 0.05 less than P less than 0.1). INH coadministration had no influence on the kinetics of oxazepam. INH impairs hepatic microsomal oxidation of triazolam, leading to reduced first‐pass hepatic extraction as well as prolonged half‐life. However INH had no influence on oxazepam conjugation.