Genetic polymorphism of S mephenytoin hydroxylation.
Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations.
Genetic polymorphism of mephenytoin p(4')-hydroxylation: difference between Orientals and Caucasians.
Hydroxylation polymorphism of debrisoquine and mephenytoin
in European populations.
The half-life of mephenytoin
is about 7 hours with biotransformation yielding an active metabolite, nirvanol, which has its own half-life of 95-144 hours.
Family study of a genetically determined deficiency of mephenytoin hydroxylation in man.
Mephenytoin and sparteine pharmacogenetics in Canadian Caucasians.
Other drugs assayed at therapeutic concentrations that had no interference included carbamazepine and its epoxide and hydroxy metabolites, oxcarbazepine and it monohydroxylated metabolite, zonisamide, levetiracetam, phenytoin and its metabolites, felbamate, lamotrigine, clonazepam, phenobarbital, primidone, acetaminophen, salicylate, ibuprofen, amitriptyline, nortriptyline, desipramine, doxepin and nordoxepin, imipramine, valproic acid, topiramate, mephenytoin
and Nirvanol, amiodarone and desethylamiodarone, methsuximide and normethsuximide, ethotoin, clozapine, and sertraline.
The major genetic defect responsible for the polymorphism of S mephenytoin
metabolism in humans.
A genetic polymorphism in the metabolism of the anticonvulsant drug mephenytoin in humans is a prime example of interracial and individual variability in drug metabolism.
Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*28) in a Caucasian poor metabolizer of mephenytoin.
An additional defective allele, CYP2C19*5, contributes to the S mephenytoin poor metabolizer phenotype in Caucasians.
Cytochrome P450 Gene family isoenzymes Representative substrates CYP1 P450IA2 Caffeine, theophylline CYP2 P450IIC19 Mephenytoin
, phenylbutazone P450IID6 Debrisoquin, metoprolol P450IIE1 Ethanol, acetaminophen CYP3 P450IIIA4 Erythromycin, cyclosporine Table 3.
A second well-characterized CYP-related drug metabolism polymorphism in humans is associated with the 4'-hydroxylation of the S-enantiomer of the anticonvulsant mephenytoin .
Recent studies have shown that CYP2C19 is the enzyme primarily responsible for the 4'-hydroxylation of mephenytoin in humans [60,61].