Mephenytoin 4 -hydroxylation

Daniel, H. I. Edeki, T. I. (1996). Genetic polymorphism of S-mephenytoin 4 -hydroxylation. Psychopharmacol. Bull, 32, 219-30. 

Inoue, K. et al. (1997). Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4 -hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics, 7, 103-13. 

Xie HG, Kim RB, Stein CM, Wilkinson GR, Wood AJJ. Genetic polymorphism of (S)-mephenytoin 4 -hydroxylation in populations of African descent. Br J Clin Pharmacol 1999 48 402-408. 

Wrighton SA, Stevens JC, Becker GW. Isolation and characterization of human liver cytochrome P4502C19 correlation between 2C19 and S-mephenytoin 4 -hydroxylation. Arch Biochem Biophys 1993 306 240-245. 

Sohn DR, Kwon JT, Kim HK, et al. Metabolic disposition of lansoprazole in relation to the S-mephenytoin 4 -hydroxylation phenotype status. Clin Pharmacol Ther 1997 61 574-582. 

Chiba K, Kobayashi K, Manabe K, et al. Oxidative metabolism of omeprazole in human liver microsomes cosegregation with S-mephenytoin 4,-hydroxylation. J Pharmacol Exp Ther 1993 266 52-59. 

Setiabudy R, Kusaka M, Chiba K, et al. Metabolic disposition of proguanil in extensive and poor metabolisers of S-mephenytoin 4 -hydroxylation recruited from an Indonesian population. Br J Clin Pharmacol 1995 39 297-303. 

CYP2C18/ 2C19 Liver CYP2C19 2 CYP2C19 3 (S)-mephenytoin 4 -hydroxylation (preferred1) Ticlopidine (acceptable1, also inhibits CYP2D6) Ketoconazole Rifampicine Carbamazepine < 5%... 

Koyama E, Tanaka T, Chiba K, et al Steady-state plasma concentrations of imipramine and desipramine in relation to S-mephenytoin 4 -hydroxylation status in Japanese depressive patients. J Clin Psycho-pharmacol 16 286-293,1996... 

C. Toyoki, T. Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4 -hydroxylation. Clin.Pharmacol.Ther., 1995, 58, 155-164... 

Knodell, R.G., R.K. Dubey, G.R. Wilkinson, and EP. Guengerich (1988). Oxidative metabolism of hexobarbital in human liver Relationship to polymorphic S-mephenytoin 4-hydroxylation. J. Pharmacol. Exp. Then 245, 845-849. 

S. J. Coulter, B. Chanas, E.F. Johnson et al. (2001). Identification of human CYP2C19 residues that confer 5-mephenytoin 4 -hydroxylation activity to CYP2C9. Biochemistry AO, 1937-1944. 

C19 (5)Mephenytoin 4 -hydroxylation Phenobarbital Rifampin (+)-N-3 -Benzyl-nirvanoF" (+)-N-3 -Benzyl-phenobarbitaF" Ticlopidine"" S-Mephenytoin ... 

FIGURE 16.1 Hyperbolic saturation curve of CYP2C19-catalyzed (5)-mephenytoin 4 -hydroxylation in human liver microsomes. Am and Vmax values were calculated with Equation 16.1 (Am = 23.7 2.15 jlM and Fmax = 0.36 0.01 nmol/min/mg). Data were fitted by nonlinear regression (Eq. 16.1, SigmaPlot 9.0). 

FIGURE 16.5 Celecoxib inhibition of CYP2C19-catalyzed (5)-mephenytoin 4 -hydroxylation in human liver microsomes Y ax = 0.40 0.02 nmol/min/mg, = 13.8 1.9 xM, Ki = 3.2 0.4 xM, RSS = 0.002, and = 0.981, respectively. All kinetic values were determined by multiple nonlinear regression (3-dimension) using the velocity equation of competitive inhibition in Table 16.3. 

Neither P450 2C19 nor (5)-mephenytoin 4 -hydroxylation activity was detected in fetal liver samples [689]. 

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