Table 3.

Bioequivalence testing of the 1.25 and 2.5 mg doses of tibolone.

	Comparison of 1.25 mg tablet (test) vs 2.5 mg (reference) for tibolone and its metabolites
	Tibolone			Δ4-isomer			3α-hydroxy tibolone			3β-hydroxy tibolone
Parameter	PE	90% CI	Res	PE	90% CI	Res	PE	90% CI	Res	PE	90% CI	Res
dn-Cmax	1.32	1.14, 1.54	NB	1.04	0.91, 1.18	B	1.27	1.15, 1.40	NB	1.17	1.07, 1.28	NB
tmax	0.73	0.59, 0.90	NB	0.79	0.66, 0.94	NB	0.73	0.60, 0.89	NB	0.88	0.73, 1.05	I
dn-AUC(0,tfix)							1.08	1.04, 1.14	B	1.07	1.01, 1.14	B
dn-AUC(0,∞)							1.08	1.03, 1.13	B	1.04	0.96, 1.12	B
CL/F kg−1							0.92	0.88, 0.97	B	0.96	0.89, 1.04	B
t½							1.04	1.00, 1.09	B	1.01	0.91, 1.13	B

PE: Point estimate of parameter ratio; 90% CI: 90% confidence interval of parameter ratio; Res: Result; (N)B: (not) bioequivalent ((not) bioequivalent means 90% confidence interval (not) contained within 0.80, 1.25); I: indeterminent due to large variation; dn-C_max=dose-normalized maximum concentration of drug in plasma; t_max = time to maximum concentration of drug in plasma; dn-AUC(0,t_fix)=dose-normalized area under the plasma concentration-time curve from time 0 to t_fix: 16 h for 3α-hydroxytibolone and 8 h for 3β-hydroxytibolone; dn-AUC(0,∞)=dose-normalized 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. n = 31, except for the following: C_max and t_max of the Δ⁴-isomer (n = 30, because in one subject, all measured plasma concentrations following administration of tibolone 1.25 mg were below the lower limit of quantification) and AUC(0,8 h), AUC(0,∞), CL/F kg⁻¹, and t_½ of 3β-hydroxy tibolone (n=24, because of the absence of a terminal linear phase in subjects' plasma concentration-time plots following administration of tibolone 1.25 mg).