Metabolic Pathways | CYP1A1 | CYP1A2 | CYP2C8 | CYP2C9 | CYP2C19 | CYP2D6 | CYP3A4 | CYP3A5 |
---|---|---|---|---|---|---|---|---|
HAL → HTP | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 3.18 ± 0.12 | N.D. |
HAL → HP+ | 8.38 ± 0.01 | N.D. | N.D. | N.D. | N.D. | N.D. | 23.78 ± 1.18 | 3.30 ± 0.25 |
HAL → CPHP | 14.32 ± 0.47 | N.D. | 2.29 ± 0.13 | 1.44 ± 0.19 | 4.10 ± 0.30 | <1.001-a | 44.62 ± 1.99 | 16.50 ± 0.79 |
RH → HAL | 7.87 ± 0.74 | N.D. | N.D. | N.D. | N.D. | N.D. | 43.77 ± 2.14 | 7.01 ± 1.33 |
RH → CPHP | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 19.58 ± 4.12 | N.D. |
RH → RHP+ | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | 16.92 ± 0.49 | 2.18 ± 0.34 |
RHP+ → HP+ | 123.9 ± 3.1 | 2.55 ± 0.22 | N.D. | N.D. | N.D. | N.D. | 0.56 ± 0.12 | N.D. |
HAL (100 μM), RH (100 μM), and RHP+ (100 μM) were incubated with the recombinant P450 isoenzyme preparations for 60 min. Data are means (±S.E.M.) of three independent experiments and are presented as pmol/pmol of P450/h. With the HPLC-UV method used in the present study, the detection limit for HAL, HTP, HP+, and RHP+ (245 nm) was 0.1 μM, which enable the assay to detect a minimum enzyme activity of 0.5 pmol/pmol of P450/h. The detection limit for CPHP and RH (220 nm) was 0.2 μM, which enable the assay to detect a minimum enzyme activity of 1 pmol/pmol of P450/h.
N.D., not detected.
↵1-a Formation of CPHP from HAL was detected previously using human lymphoblast-expressed CYP2D6 and a more sensitive gas chromographic method for CPHP (Fang et al., 1997).