Table 5

NADPH-supported rates of NADPH and substrate oxidations and H2O2 formation in liver microsomes from rats untreated and orally treated with phenytoin

SubstrateProductUntreatedPhenytoin-TreatedFold Increase in Coupling Ratio
nmol/min/nmol P450
NoneOxidized NADPH13  ± 3  (100)9  ± 35-150  (100)
H2O2 2.0  ± 0.7  (15)4.2  ± 0.95-160  (22)
TestosteroneOxidized NADPH15  ± 2  (100)19  ± 3  (100)
Oxidized testosterone5-a 2.6  ± 0.4  (17)5.5  ± 0.95-160  (29)1.7
H2O2 2.3  ± 0.5  (15)3.1  ± 0.4  (16)
PhenytoinOxidized NADPH11  ± 2  (100)17  ± 35-150  (100)
Oxidized phenytoin5-b 0.15  ± 0.01  (1.4)0.04  ± 0.015-160  (0.2)0.14
H2O2 1.3  ± 0.4  (12)3.4  ± 0.75-160  (20)
4′-HPPHOxidized NADPH12  ± 3  (100)18  ± 35-150  (100)
3′,4′-diHPPH0.48  ± 0.09  (4)0.24  ± 0.035-160  (1)0.25
H2O2 1.5  ± 0.4  (13)2.3  ± 0.7  (13)

Data are mean ± S.D. for four rats. The number in parentheses indicate percentage of product formation to oxidized NADPH (coupling ratio).

  • Significantly different from untreated group (

  • 5-150p < 0.05;

  • 5-160p < 0.01).

  • 5-a  Sum of rates of 6β-, 16α-, 16β-, 2α-, and 2β-hydroxylated testosterone formation at 100 μM testosterone.

  • 5-b  Sum of rates of 4′-HPPH, 3′-HPPH, and 3′,4′-diHPPH formation at 100 μM phenytoin.