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 C max , t max , and t 1/2 of tibolone and its metabolites and on the body weight standardized oral clearance (CL/F kg x1 ) of the 3a-and 3b-hydroxy tibolones. In early postmenopausal women, significantly lower values were found for the AUC(0,16 h), and AUC(0,?) of 3a-hydroxy tibolone 24.6t6.6 vs 29.2t4.9 and 27.1t6.9 vs 32.3t6.5 ng ml x1 h for the 1.25 mg tablet, respectively, and 45.4t13.9 vs 55.7t14.1 and 49.6t14.6 vs 62.6t17.3 ng ml x1 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 3b-hydroxy tibolone. The rate of absorption of tibolone and the rates of absorption or formation of the 3a-and 3b-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-C max of tibolone and the 3a-and 3b-hydroxy tibolones, respectively. t max 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, 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.
