Ebastine hydroxylation and carebastine formation activities by recombinant P450 4F enzymes and liver and intestine microsomes from marmosets, cynomolgus monkeys, and humans
Catalytic activities were measured at the substrate concentration of 100 μM for ebastine hydroxylation. All data represent means ± S.D. of triplicate determination.
| Enzyme Source | Ebastine Hydroxylation | Carebastine Formation | ||
|---|---|---|---|---|
| nmol/min per nmol P450 | pmol/min per mg | nmol/min per nmol P450 | pmol/min per mg | |
| P450 form | ||||
| Marmoset | ||||
| 4F2 | 0.013 ± 0.001 | 0.011 ± 0.001 | ||
| 4F3B | 0.026 ± 0.003 | 0.017 ± 0.001 | ||
| 4F11 | 0.38 ± 0.04 | 0.031 ± 0.004 | ||
| 4F12 | 6.6 ± 0.4 | 1.6 ± 0.1 | ||
| Cynomolgus monkey | ||||
| 4F2 | <0.010 | <0.010 | ||
| 4F3B | 0.013 ± 0.002 | <0.010 | ||
| 4F11 | 0.94 ± 0.19 | 0.060 ± 0.008 | ||
| 4F12 | 2.8 ± 0.1 | 0.010 ± 0.001 | ||
| Human | ||||
| 4F2 | 0.081 ± 0.005 | 0.012 ± 0.001 | ||
| 4F3B | 0.043 ± 0.001 | 0.016 ± 0.001 | ||
| 4F11 | 1.1 ± 0.1 | 0.015 ± 0.001 | ||
| 4F12 | 2.5 ± 0.1 | 0.013 ± 0.001 | ||
| Microsomes | ||||
| Marmoset liver | 1460 ± 100 | 47 ± 8 | ||
| Marmoset small intestine | 602 ± 52 | 23 ± 3 | ||
| Cynomolgus monkey liver | 1170 ± 184 | 21 ± 2 | ||
| Cynomolgus monkey small intestine | 967 ± 90 | 104 ± 10 | ||
| Human liver | 405 ± 70 | 1.7 ± 0.4 | ||
| Human small intestine | 112 ± 2 | 1.5 ± 0.3 | ||