Apparent enzyme kinetic parameters for S-mephenytoin metabolism in liver microsomes from 9-week-old wt and heterozygous CYP2C18/19 transgenic mice The table shows parametric and nonparametric parameters for each group. Statistical analyses were done using the Mann-Whitney test. p values <0.05 are shown in bold.
Males | Females | ||||||
|---|---|---|---|---|---|---|---|
| wt (n = 6)a | Het (n = 8) | p value | wt (n = 6) | Het (n = 8)b | p value | ||
| Vmax (pmol/nmol P450/min) | Mean ± S.D. | 41.9 ± 11.0 | 68.8 ± 56.2 | 49.4 ± 10.5 | 40.6 ± 5.3 | ||
| Median (range) | 40.1 (29.5–58.5) | 47.0 (31.9–201.6) | 0.435 | 44.7 (40.9–66.9) | 39.9 (33.9–47.3) | 0.240 | |
| Km (μM) | Mean ± S.D. | 56.5 ± 24.4 | 53.9 ± 58.7 | 77.1 ± 19.3 | 54.8 ± 33.5 | ||
| Median (range) | 52.1 (32.3–102.6) | 28.6 (8.1–174.9) | 0.181 | 70.7 (54.9–101.7) | 50.0 (10.0–112.9) | 0.181 | |
| CLintc (μl/nmol P450/min) | Mean ± S.D. | 0.77 ± 0.25 | 2.50 ± 3.04 | 0.66 ± 0.14 | 1.51 ± 1.54 | ||
| Median (range) | 0.71 (0.52–1.11) | 1.40 (0.62–9.77) | 0.030 | 0.65 (0.44–0.85) | 0.96 (0.44–4.57) | 0.180 | |
| P450 content (nmol P450/mg mic prot) | Mean ± S.D. | 0.56 ± 0.16 | 0.35 ± 0.08 | 0.50 ± 0.09 | 0.39 ± 0.09 | ||
| Median (range) | 0.60 (0.37–0.76) | 0.33 (0.25–0.53) | 0.011 | 0.51 (0.39–0.63) | 0.41 (0.26–0.48) | 0.065 | |
| Liver weight (g) | Mean ± S.D. | 1.40 ± 0.17 | 1.24 ± 0.24 | 0.98 ± 0.04 | 0.93 ± 0.08 | ||
| Median (range) | 1.43 (1.08–1.54) | 1.21 (1.01–1.74) | 0.108 | 0.98 (0.91–1.03) | 0.95 (0.83–1.02) | 0.491 | |
| mg mic prot/g liver | Mean ± S.D. | 21.1 ± 8.21 | 25.0 ± 3.6 | 22.9 ± 3.4 | 24.0 ± 5.5 | ||
| Median (range) | 21.2 (8.3–33.9) | 25.4 (17.6–28.7) | 0.181 | 23.2 (18.7–27.9) | 24.1 (15.7–34.6) | 0.662 | |
| nmol P450/g liver | Mean ± S.D. | 12.9 ± 3.4 | 8.6 ± 1.7 | 11.4 ± 2.4 | 9.9 ± 1.9 | ||
|
| Median (range) | 12.7 (8.1–17.7) | 8.3 (7.2–12.3) |
0.019
| 11.7 (7.6–14.3) | 10.1 (7.2–11.8) | 0.180 |