Table 1

Metabolic conversion of HAL, RH, and RHP+ by CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5

Metabolic PathwaysCYP1A1CYP1A2CYP2C8CYP2C9CYP2C19CYP2D6CYP3A4CYP3A5
HAL → HTPN.D.N.D.N.D.N.D.N.D.N.D.3.18 ± 0.12N.D.
HAL → HP+ 8.38 ± 0.01N.D.N.D.N.D.N.D.N.D.23.78 ± 1.183.30 ± 0.25
HAL → CPHP14.32 ± 0.47N.D.2.29 ± 0.131.44 ± 0.194.10 ± 0.30<1.001-a 44.62 ± 1.9916.50 ± 0.79
RH → HAL7.87 ± 0.74N.D.N.D.N.D.N.D.N.D.43.77 ± 2.147.01 ± 1.33
RH → CPHPN.D.N.D.N.D.N.D.N.D.N.D.19.58 ± 4.12N.D.
RH → RHP+ N.D.N.D.N.D.N.D.N.D.N.D.16.92 ± 0.492.18 ± 0.34
RHP+ → HP+ 123.9 ± 3.12.55 ± 0.22N.D.N.D.N.D.N.D.0.56 ± 0.12N.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).