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Dose proportionality of three different doses of tibolone
Cees J Timmer1, Natalie S Houwing
1Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands. cees.timmer@organon.com
Study Objective:
To assess dose proportionality of tibolone tablets after multiple oral administration.
Design:
Open-label, randomized, three-period crossover study
Setting:
Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands.
Subjects:
Twenty-seven postmenopausal women aged 65 years or younger.
Intervention:
Subjects received tibolone 1.25, 2.5, or 5.0 mg once/day for 7 days.
Measurements And Main Results:
Plasma concentrations of tibolone and its three primary metabolites were assayed. Steady state was attained by day 5. Elimination half-life for 3alpha-hydroxytibolone was 7.2-8.5 hours. At steady state, the dose-normalized peak concentration and area under the curve satisfied bioequivalence requirements for the 1.25- and 2.5-mg doses, but not fully for the 5.0-mg dose. Parameters were proportionally slightly lower for the 5.0-mg dose compared with the 1.25- and 2.5-mg doses.
Conclusion:
Proportional bioequivalence was established for the 1.25- and 2.5-mg doses, but not between the 5.0-mg dose and the two lower doses of tibolone.