Intrinsic clearance values for NVS-CRF38 and [13CD3]NVS-CRF38 in liver microsomes
Intrinsic clearance values were determined by either substrate depletion or metabolite formation in mixed-gender human or male Sprague-Dawley rat liver microsomes. The initial substrate concentration was 100 nM and the microsomal protein concentration was 0.8 mg/ml. The cofactor NADPH was included to activate cytochrome P450 enzymes. Data are the mean and S.D. of three determinations.
| Substrate | Intrinsic Clearance | |||
|---|---|---|---|---|
| Depletion | Formation | |||
| Rat | Human | Rat | Human | |
| ml/min/kg microsomal protein | ml/min/kg microsomal protein | ml/min/kg microsomal protein | ml/min/kg microsomal protein | |
| NVS-CRF38 | 32.9 ± 3.6 | 17.2 ± 2.8 | 18.2 ± 6.9 | 4.4 ± 1.0 |
| [13CD3] NVS-CRF38 | 15.8 ± 4.7 | 10.7 ± 2.8 | 2.5 ± 0.4 | 0.85 ± 0.34 |
| KH/KD | 2.2 ± 0.8 | 1.7 ± 0.5 | 7.1 ± 2.1 | 5.4 ± 0.9 |