Effect of renal impairment on the pharmacokinetics of a single oral dose of tibolone 2.5 mg in early postmenopausal women.
OBJECTIVE
To determine the influence of renal function on the pharmacokinetics of tibolone and its primary metabolites, delta4-tibolone, 3alpha-hydroxytibolone, and 3beta-hydroxytibolone.


METHODS
Open-label, single-center, single-dose study


METHODS
Drug research center, Balatonfüred, Hungary.


METHODS
Twenty-four postmenopausal women aged 45-65 years.


METHODS
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.


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.


CONCLUSIONS
Pharmacokinetic parameters of tibolone were not affected by varying degrees of renal function.
Timmer
Cees J
CJ
Department of Drug Metabolism and Kinetics, N.V. Organon, Oss, The Netherlands. cees.timmer@organon.com
Doorstam
Dennis P
DP
D000368:Aged; D019540:Area Under Curve; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008593:Menopause / Q000097:blood* / Q000187:drug effects; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000097:blood*
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; C027385:tibolone