Tibolone

Following oral administration, tibolone is rapidly metabolised into three compounds, which all contribute to the pharmacodynamic profile of tibolone. Two of the metabolites (3α-OH-tibolone and 3β-OH-tibolone) have oestrogenic-like activities, whereas the third metabolite (4Δ-isomer of tibolone) has progestogenic and androgenic-like activities.

Tibolone substitutes for the loss of oestrogen production in postmenopausal women and alleviates menopausal symptoms. Tibolone prevents bone loss following menopause or ovariectomy.

Absorption and biotransformation

Following oral administration, tibolone is rapidly and extensively absorbed. Due to rapid metabolism, the plasma levels of tibolone are very low. The plasma levels of the Δ4-isomer of tibolone are also very low. Therefore some of the pharmacokinetic parameters could not be determined. Peak plasma levels of the 3α-OH and the 3β-OH metabolites are higher but accumulation does not occur.

Table 5. Pharmacokinetic parameters of Tibolone (2.5 mg):

SD = single dose ; MD = multiple dose

Elimination

Excretion of tibolone is mainly in the form of conjugated (mostly sulfated) metabolites. Part of the administered compound is excreted in the urine, but most is eliminated via the faeces.

The consumption of food has no significant effects on the extent of absorption.

Other special populations

The pharmacokinetic parameters for tibolone and its metabolites were found to be independent of renal function.

In animal studies, tibolone had anti-fertility and embryotoxic activities by virtue of its hormonal properties. Tibolone was not teratogenic in mice and rats. It displayed teratogenic potential in the rabbit at near-abortive dosages. Tibolone is not genotoxic under in vivo conditions. Although a carcinogenic effect was seen in certain strains of rat (hepatic tumours) and mouse (bladder tumours), the clinical relevance of this is uncertain.