Predicted CLint and CLh values and clinical reference data
In vitro half-life (t1/2) 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 CLh values are provided in Supplemental Table 2.
Observed CLh | Individual Spheroids | Pooled Spheroids | |||||||
---|---|---|---|---|---|---|---|---|---|
t1/2 | CLint | CLh | P | t1/2 | CLint | CLh | P | ||
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 |