Metabolic stability of test compounds in liver microsomes and cDNA-expressed human P450 enzymes: contribution of specific P450 enzymes to in vitro metabolism
Human Liver Microsomes Percentage Inhibition by Ketoconazolea | cDNA-Expressed Human P450s Relative Percentage of Metabolite(s) to Total Drug-Related UV Peaksb | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1A2 | 2C9 | 2C19 | 2D6 | 3A4 | ||||||
| BMS-1 | 95 | 0 | <1.0 | 0 | <0.2 | 14.2 | ||||
| BMS-2 | 72 | 0 | 4.3 | 0 | <0.2 | 9.3 | ||||
| BMS-3 | 53 | 0 | 8.3 | <0.02 | <0.2 | 6.2 | ||||
↵ a Percentage inhibition was estimated by comparing the percentage loss of the test compounds at 0- and 5-min incubation of test compounds in the presence and absence of ketoconazole (2 μM).
↵ b Relative percentage of metabolite(s) was estimated by combining all the detectable metabolite peaks by LC/UV and comparing that with the total UV absorbance for all the drug-related peaks at λ = 280 nm.