A methodological investigation on the estimation of the S-mephenytoin hydroxylation phenotype using the urinary S/R ratio.
After a single oral dose of racemic mephenytoin the S/R ratio in urine can be used to phenotype extensive (EM) and poor metabolizers (PM) of S-mephenytoin. We confirmed the increased S/R ratio by storage time in EM because of the hydrolysis of a conjugate of S-mephenytoin excreted in EM, but not in PM. The S/R ratio in the 0-8 h urine increased 8- to 127-fold (from 0.22 +/- 0.16 to 9.9 +/- 11.3) after acid treatment of urine from 30 EM, but there was no effect of acid in that of 12 PM. We suggest that the phenotype of mephenytoin in combination with debrisoquine can be determined in the 0-8 h urine by estimating the mephenytoin S/R ratio before and after acid treatment.
Tybring
G
G
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Bertilsson
L
L
D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D008617:Mephenytoin / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D013237:Stereoisomerism
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D008617:Mephenytoin