Dose proportionality of three different doses of tibolone.
OBJECTIVE
To assess dose proportionality of tibolone tablets after multiple oral administration.


METHODS
Open-label, randomized, three-period crossover study


METHODS
Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands.


METHODS
Twenty-seven postmenopausal women aged 65 years or younger.


METHODS
Subjects received tibolone 1.25, 2.5, or 5.0 mg once/day for 7 days.


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.


CONCLUSIONS
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.
Timmer
Cees J
CJ
Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands. cees.timmer@organon.com
Houwing
Natalie S
NS
D000284:Administration, Oral; D000368:Aged; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D009426:Netherlands; D009652:Norpregnenes / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; C027385:tibolone