Table 2.

Pharmacokinetic parameters (mean ± s.d.) for tibolone and its metabolites in early and late postmenopausal women.

		Tibolone 1.25 mg		Tibolone 2.5 mg
Compound measured	Parameter	Early	Late	Early	Late
Tibolone	Cmax (ng ml−1)	0.9±0.3	1.1±0.4	1.5±0.7	1.6±0.8
	tmax (h)	1.0±0.7	0.9±0.7	1.3±0.7	1.1±0.6
Δ4-isomer	Cmax (ng ml−1)	0.3±0.1	0.3±0.1	0.4±0.2	0.8±1.1
	tmax (h)	1.6±0.8	1.3±0.8	1.8±1.4	1.9±1.3
3α-hydroxy tibolone	Cmax (ng ml−1)	8.3±2.9a	10.9±3.3	14.6±5.4	16.7±6.6
	tmax (h)	1.2±0.7	0.9±0.7	1.3±0.6	1.3±0.6
	AUC(0,16 h) (ng ml−1 h)	24.6±6.6a	29.2±4.9	45.4±13.9a	55.7±14.1
	AUC(0,∞) (ng ml−1 h)	27.1±6.9a	32.3±6.5	49.6±14.6a	62.6±17.3
	CL/F kg−1 (l h−1 kg−1)	0.74±0.15	0.70±0.17	0.83±0.2	0.75±0.25
	t½ (h)	6.4±1.0	5.9±1.6	5.7±0.6	6.0±1.2
3β-hydroxy tibolone	Cmax (ng ml−1)	2.1±0.6	2.1±0.8	3.8±1.4	3.7±2.0
	tmax (h)	1.4±0.6	1.2±0.6	1.6±0.9	1.5±0.8
	AUC(0,8 h) (ng ml−1 h)	6.2±1.8	5.7±1.4	11.7±3.6	10.9±2.8
	AUC(0,∞) (ng ml−1 h)	8.7±2.2b	8.5±1.9b	15.9±4.4	15.5±4.3
	CL/F kg−1 (l h−1 kg−1)	2.29±0.41b	2.71±0.84b	2.58±0.68	3.04±1.08
	t½ (h)	6.2±2.8b	6.2±1.3b	6.4±1.8	5.9±1.9

C_max=maximum concentration of drug in plasma; t_max=time to maximum concentration of drug in plasma; AUC(0,8 h) and AUC(0,16 h) = area under the plasma concentration-time curve from time 0–8 h or 0 to16 h, respectively; AUC(0,∞) = area under the plasma concentration-time curve from time 0 to infinity; CL/F kg⁻¹ = oral clearance per kg body weight; t_½=elimination half-life

^aP < 0.05, early vs late postmenopausal women

^bn=12; for all other assessments n = 15–16.