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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(-1)) of the 3alpha- and 3beta-hydroxy tibolones. In early postmenopausal women, significantly lower values were found for the AUC(0,16 h), and AUC(0, infinity ) of 3alpha-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, infinity) of 3beta-hydroxy tibolone. The rate of absorption of tibolone and the rates of absorption or formation of the 3alpha- and 3beta-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 3alpha- and 3beta-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, infinity) and the AUC(0,t(fix)) values for the 3alpha-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 3beta-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 t(1/2)., 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.

Study Objective: To determine the influence of renal function on the pharmacokinetics of tibolone and its primary metabolites, delta4-tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone., Design: Open-label, single-center, single-dose study, Setting: Drug research center, Balatonfüred, Hungary., Subjects: Twenty-four postmenopausal women aged 45-65 years., Intervention: Subjects were assigned to one of four groups based on their renal function, as assessed by glomerular filtration rate (normal to severely impaired), and received a single dose of tibolone 2.5 mg. Pharmacokinetic parameters of tibolone and its primary metabolites were derived from blood samples taken at predefined intervals for up to 48 hours after tibolone administration. Pharmacokinetic parameters were calculated using standard noncompartmental methods and compared by analysis of covariance., Measurements and Main Results: Pharmacokinetic parameters of tibolone and its primary metabolites were similar in subjects with normal to severely impaired renal function. Pharmacokinetic profiles of tibolone and its metabolites were independent of the degree of renal impairment., Conclusion: Pharmacokinetic parameters of tibolone were not affected by varying degrees of renal function.