Mephenytoin hydroxylation deficiency in Caucasians: Frequency of a new oxidative drug metabolism polymorphism

Abstract

The ability of normal subjects to hydroxylate mephenytoin (100 mg) or debrisoquine (10 mg) after oral dosing was investigated in 156 unrelated Caucasians living in middle Tennessee. Urinary recovery of 4-hydroxymephenytoin (4-OH-M) and the urinary S:R enantiomeric ratio of mephenytoin measured in an 8-hr urine sample were investigated as phenotypic traits for mephenytoin, and the urinary metabolic ratio of debrisoquine was used to determine the debrisoquine hydroxylase phenotype. Both urinary 4-OH-M and the S:R ratio of mephenytoin discriminated between extensive (EM) and poor (PM) metabolizers of mephenytoin. The frequencies of PMs for mephenytoin and debrisoquine hydroxylation activity were 2.6% and 7.0%. These two defects in oxidative metabolism were not observed in the same subjects, which suggests that 4-hydroxylation of mephenytoin is a new polymorphism independent of that for debrisoquine.

Effect of omeprazole 10 mg on intragastric pH in three different CYP2C19 genotypes, compared with omeprazole 20 mg and lafutidine 20 mg, a new H2‐receptor antagonist

“…42,45 Now these results can be clearly explained by interethnic variations in the CYP2C19 genotype. Among North American and European populations, 56.7-81.0% of patients are homo-EMs, 18.0-37.2% are hetero-EMs, and PMs are less than 6.1%, [46][47][48][49][50] and thus omeprazole 40 mg is required to achieve stronger gastric acid suppression than H 2 -RAs. However, in Orientals, homo-EMs are only 27.7-38.2% and the rest of the population has an intermediate or reduced capacity to metabolize omeprazole; 30,[51][52][53] and therefore strong gastric acid suppression can be obtained even with omeprazole 20 mg or less.…”

Morphine or Oxycodone in Cancer Pain?

“…A debrisoquine test to determine the CYP2D6 phenotype was performed following the method by Wedlund et al (10). Oxymorphone was analyzed by G.C.…”

Genetic analysis of the cytochrome P‐450IIC18 (CYP2C18) gene and a novel member of the CYP2C subfamily

“…The human CYP2C subfamily consists of at least 4 members (CYP2C8, CYP2C9, CYP2C18, CYP2C19) [1,2]. Extensive metabolizer (EM) and poor metabolizer (PM) polymorphism for mephenytoin [3,4] is well known and has been studied extensively. It has been shown that CYP2C19 is a candidate for mephenytoin 4'-hydroxylation [5,6].…”