TABLE 1

Predicted CL_int and CL_h values and clinical reference data

In vitro half-life (t_1/2) is expressed in [h]. Clearance values are expressed in [mL/min/kg] and refer to blood elimination. Data represent mean values ± S.D. obtained using hepatocyte spheroids from donors A, B, and C (apixaban, carbamazepine, clozapine, olanzapine) or mean values ± S.D. obtained using hepatocyte spheroids from donor C in two independent experiments (nortriptyline, risperidone, venlafaxine). Literature references for clinical CL_h values are provided in Supplemental Table 2.

	Observed CL_h	t_1/2	CL_int	CL_h	P	t_1/2	CL_int	CL_h	P
	Observed CL_h	Individual Spheroids			Pooled Spheroids
Apixaban	0.576	1003.1 ± 432.1	2.78 ± 1.47	0.434 ± 0.224	<0.05	1463.7 ± 1202.6	0.244 ± 0.158	0.0389 ± 0.0251	<0.05
Carbamazepine	0.110	2149.2 ± 310.9	1.12 ± 0.162	0.254 ± 0.0363	N.S.	1464.5 ± 1365.4	0.289 ± 0.229	0.0661 ± 0.0524	<0.05
Clozapine	2.19	83.4 ± 21.5	29.7 ± 6.69	1.64 ± 0.344	<0.0001	13.7 ± 8.52	21.5 ± 9.96	1.21 ± 0.537	<0.0001
Olanzapine	3.55	196.4 ± 91.8	13.8 ± 5.52	1.28 ± 0.488	<0.05	90.0 ± 12.1	2.67 ± 0.378	0.264 ± 0.0368	<0.0001
Nortriptyline	6.68	27.0 ± 0.247	87.9 ± 0.799	3.00 ± 0.0234	<0.0001
Risperidone	7.74	48.5 ± 2.64	49.0 ± 2.91	5.59 ± 0.233	<0.0001
Venlafaxine	8.79	135.1 ± 11.1	37.5 ± 0.746	4.77 ± 0.244	<0.0001