Pharmacokinetics of tibolone in early and late postmenopausal women

Publisher Website
Google Scholar
Abstract
Aims  Tibolone is a tissue‐specific compound with favourable effects on bone, vagina, climacteric symptoms, mood and sexual well being in postmenopausal women, without stimulating the endometrium or breast. Since tibolone is used for the treatment of both young and elderly postmenopausal women, its pharmacokinetics were studied to investigate potential differences with age. In addition, the bioequivalence of the 1.25 and 2.5 mg tablets was evaluated.Methods  Single doses of 1.25 or 2.5 mg of tibolone were given in a double‐blind, randomized, two‐way cross‐over study to women aged between 45 and 55 years or between 65 and 75 years of age.Results  Age did not have a significant effect on Cmax, tmax, and t½ of tibolone and its metabolites and on the body weight standardized oral clearance (CL/F kg−1) of the 3α‐ and 3β‐hydroxy tibolones. In early postmenopausal women, significantly lower values were found for the AUC(0,16 h), and AUC(0,∞) of 3α‐hydroxy tibolone 24.6±6.6 vs 29.2±4.9 and 27.1±6.9 vs 32.3±6.5 ng ml−1 h for the 1.25 mg tablet, respectively, and 45.4±13.9 vs 55.7±14.1 and 49.6±14.6 vs 62.6±17.3 ng ml−1 h for the 2.5 mg tablet, respectively. When these values were adjusted for the significantly higher body weight of the early postmenopausal women, the differences disappeared. No significant differences between early and late postmenopausal women were found for the AUC(0,8 h), and AUC(0,∞) of 3β‐hydroxy tibolone. The rate of absorption of tibolone and the rates of absorption or formation of the 3α‐ and 3β‐hydroxy tibolones were significantly higher after the 1.25 mg dose than after the 2.5 mg tablet, resulting in increases of 32%, 27% and 17% for the dose normalized‐Cmax of tibolone and the 3α‐ and 3β‐hydroxy tibolones, respectively. tmax for tibolone and its metabolites was 12–27% less after 1.25 mg compared to 2.5 mg, which was statistically significant. The two formulations were bioequivalent with respect to the dose‐normalized AUC(0,∞) and the AUC(0,tfix) values for the 3α‐hydroxy tibolone (ratio point estimate [90%, confidence limits]: 1.08 [1.04, 1.14] and 1.08 [1.03, 1.13], respectively) and for the 3β‐hydroxy tibolone (1.07 [1.01, 1.14] and 1.04 [0.96, 1.12], respectively). Both formulations were also bioequivalent with respect to CL/F kg−1 and t½.Conclusions  The pharmacokinetics of tibolone are similar in early (age 45–55 years) and late (65–75 years) postmenopausal women. The 2.5 and 1.25 mg tablets are bioequivalent with respect to the extent of absorption. The rate of absorption or formation of the metabolites of tibolone were not bioequivalent, but these differences are considered to have no clinical relevance in view of the chronic administration of tibolone.

This publication has 10 references indexed in Scilit: