Table 2

Ki values for the inhibition of CYP2C19 by mephenytoin, N-3-benzyl-nirvanol, and N-3-benzyl-phenobarbital enantiomers

CompoundKiInhibitor Potency Relative to (S)-Mephenytoin
μM
(R)-(−)-Mephenytoin237.00.12
(S)-(+)-Mephenytoin29.51.0
(−)-N-3-Benzyl-nirvanol5.35.6
(+)-N-3-Benzyl-nirvanol0.25118.0
(+)-N-3-Benzyl-phenobarbital4.76.3
(−)-N-3-Benzyl-phenobarbital0.079373.0

CYP2C19 activity was measured as MFL demethylation using reconstituted recombinant enzymes, as described under Materials and Methods. Ki values were determined by nonlinear regression with SYSTAT Statistics ver 5.0 using the competitive inhibition equation. Data are expressed as means of two or three experiments.