The inhibition of SKF525A metabolism by P450 isoform-selective inhibitors SKF525A (100 μM) was incubated in the presence and absence of an isoform-selective inhibitor with NADPH-fortified human liver microsomes (a 1 mg/ml mix of six commercial preparations) for 15 min. The results are the mean of two independent incubations with the superscript indicating the ±range (to the nearest integer).
Inhibitor (and Targeted P450 Isoform) | Determined IC50 for Prototype Substrate | Inhibition of SKF8742 Formation at: | ||
|---|---|---|---|---|
| IC50 for Prototype Substrate | >>IC50 | |||
| μM | %a | %/[μM] | ||
| α-Naphthoflavone (CYP1A2) | 0.4 | 64a | 50a [4] | |
| Tranylcypromine (CYP2A6/CYP2C19) | 2.5 | 13a | 52 [25] | |
| 4-(4-Chlorobenzyl)pyridine (CYP2B6) | 0.3 | 40 | 93 [1.25] | |
| Sulfaphenazole (CYP2C9) | 0.2 | 73a | 72a [6] | |
| Quinidine (CYP2D6) | 0.1 | 156a | 44a [0.5] | |
| Ketoconazole (CYP3A4/5) | 0.03 | 351 | 781 [0.3] | |
↵ a An “a” following the number indicates activation rather than inhibition