Dose Proportionality of Three Different Doses of Tibolone

• Published in: Pharmacotherapy 2002-01, Vol.22 (1), p.6-13
• Main Authors: Timmer, Cees J., Houwing, Natalie S.
• Format: Article
• Language: English
• Subjects: 3^a-Hydroxytibolone; Administration, Oral; Aged; Biological and medical sciences; Cross-Over Studies; Drug Administration Schedule; Estrogen Receptor Modulators - administration & dosage; Estrogen Receptor Modulators - blood; Estrogen Receptor Modulators - pharmacokinetics; Female; Half-Life; Humans; Medical sciences; Middle Aged; Miscellaneous; Netherlands; Norpregnenes - administration & dosage; Norpregnenes - blood; Norpregnenes - pharmacokinetics; Pharmacology. Drug treatments; Tibolone
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1592/phco.22.1.6.33495

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 3α‐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.