ABSTRACT
STUDY OBJECTIVE: To assess the effect of food on absorption and pharmacokinetic disposition of tibolone. DESIGN: Open-label, randomized, crossover study with a 1-week washout period. SETTING: Institut für Klinische Pharmakologie, Hohenkirchen-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, delta4-tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone, were assayed by gas chromatography with mass spectrometry. Peak plasma concentration (Cmax), time to Cmax, area under the plasma concentration versus time curve from time zero to infinity (AUC(0-infinity)), and elimination half-life were calculated, and food effects were evaluated. Plasma concentrations of tibolone and delta4-tibolone were too low to estimate AUC(0-infinity) and half-life. Absorption or formation of 3alpha-hydroxytibolone and 3beta-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-infinity) or half-life for 3alpha-hydroxytibolone and 3beta-hydroxytibolone. CONCLUSION: Food consumption decreased and delayed Cmax but had no effect on the exposure of tibolone and its metabolites. Tibolone therefore can be administered irrespective of meal timing.
