Effect of renal impairment on the pharmacokinetics of a single oral dose of tibolone 2.5 mg in early postmenopausal women

Abstract

Study Objective. To determine the influence of renal function on the pharmacokinetics of tibolone and its primary metabolites, Δ4-tibolone, 3α-hydroxytibolone, and 3β-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.