Effect of a standardized meal on the bioavailability of a single oral dose of tibolone 2.5 mg in healthy postmenopausal women.
OBJECTIVE
To assess the effect of food on absorption and pharmacokinetic disposition of tibolone.


METHODS
Open-label, randomized, crossover study with a 1-week washout period.


METHODS
Institut für Klinische Pharmakologie, Hohenkirchen-Siegertsbrunn, Germany


METHODS
Twenty-four healthy, early postmenopausal women.


METHODS
Single doses of tibolone 2.5 mg were administered after subjects consumed a high-fat meal or fasted.


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.


CONCLUSIONS
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.
Timmer
Cees J
CJ
Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands. cees.timmer@organon.com
Huisman
Johannes A M
JA
D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D017698:Postmenopause / Q000097:blood / Q000378:metabolism
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; C027385:tibolone