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Effect of a Standardized Meal on the Bioavailability of a Single Oral Dose of Tibolone 2.5 mg in Healthy Postmenopausal Women
Author(s) -
Timmer Cees J.,
Huisman Johannes A. M.
Publication year - 2002
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.22.5.310.33186
Subject(s) - tibolone , bioavailability , meal , cmax , pharmacokinetics , crossover study , medicine , endocrinology , chemistry , pharmacology , postmenopausal women , alternative medicine , pathology , placebo
Study Objective. To assess the effect of food on absorption and pharmaco‐kinetic disposition of tibolone. Design. Open‐label, randomized, crossover study with a 1‐week washout period. Setting. Institut für Klinische Pharmakologie, Höhenkirchen‐Siegertsbrunn, Germany. Subjects. Twenty‐four healthy, early postmenopausal women. Intervention. Single doses of tibolone 2.5 mg were administered after subjects consumed a high‐fat meal or fasted. Measurements and Main Results. Plasma concentrations of tibolone and its three primary metabolites, Δ 4 ‐tibolone, 3α‐hydroxytibolone, and 3β‐hydroxytibolone, were assayed by gas chromatography with mass spectrometry. Peak plasma concentration (C max ), time to C max , area under the plasma concentration versus time curve from time zero to infinity (AUC 0‐∞ ), and elimination half‐life were calculated, and food effects were evaluated. Plasma concentrations of tibolone and Δ 4 ‐tibolone were too low to estimate AUC 0‐∞ and half‐life. Absorption or formation of 3α‐hydroxytibolone and 3β‐hydroxytibolone was slower in fed participants than in fasting participants, but this was of no clinical relevance because of the long‐term nature of tibolone treatment. Meal consumption did not affect AUC 0‐∞ or half‐life for 3α‐hydroxytibolone and 3β‐hydroxytibolone. Conclusion. Food consumption decreased and delayed C max but had no effect on the exposure of tibolone and its metabolites. Tibolone therefore can be administered irrespective of meal timing.