Genetic polymorphism of mephenytoin p(4′)‐hydroxylation: difference between Orientals and Caucasians.

Abstract

The genetically controlled mephenytoin p(4′)‐hydroxylation capacity was determined in 118 Caucasians and 70 Orientals. After an oral dose of 50 or 100 mg of racemic mephenytoin, the amount of p(4′)‐ hydroxymephenytoin in 24 h urine was measured by gas chromatography. Bimodal distribution was found with 9/70 (13%) Orientals and 5/118 (4%) Caucasians demonstrating deficient p(4′)‐hydroxylation. The statistically significant difference between Orientals and Caucasians (P less than 0.05) was accounted for by the high incidence of poor metabolizers among the Japanese subjects, 7/31 (23%). The frequency among Chinese subjects, 2/39 (5%), was similar to the frequency among Caucasians.

Evidence for polymorphic oxidation of sparteine in Japanese subjects.

“…Compared with Caucasians where 40 to 50% are rapid acetylators, as much as 90% of the Japanese belong to the rapid acetylator phenotype (Sunahara et al, 1961). The frequency of PMs of mephenytoin wag reported to be 18% (Nakamura et al, 1985) and 22.6% (Jurima et al, 1985) in a Japanese population, whereas it was 2.7% in a white American (Nakamura et al, 1985) and 4.2% (Jurima et al, 1985) in a Canadian population. However, no PMs of debrisoquine were observed among the 100 Japanese subjects studied by Nakamura et al (1985).…”

Caution in the use of a 100 mg dose of racemic mephenytoin for phenotyping southeastern Oriental subjects [letter]

“…They are PMs according to either of the criteria normally used (Horai et al, 1989;Jurima et al, 1985;Kupfer & Preisig, 1984). The remaining eight subjects (seven were EMs and one was a PM had only minor complaints (e.g., dizziness) after the mephenytoin dose.…”

Metabolism of 18-Methoxycoronaridine, an Ibogaine Analog, to 18-Hydroxycoronaridine by Genetically Variable CYP2C19

“…Mephenytoin has low affinity for CYP2C19 (K m values ranging from 59 -143 M) (Jurima et al, 1985), and its CYP2C19-dependent metabolic ratio has been shown to change with long-term storage of samples (Zhang et al, 1991;Tamminga et al, 2001), whereas the formation of 5-hydroxyomeprazole from omeprazole has been shown to be mediated by CYP2C19 as well as CYP3A4 (Andersson et al, 1993). In vivo studies will be needed to determine whether 18-MC can be used as an in vivo CYP2C19 probe substrate.…”

“…The poor metabolizer (PM) phenotype, constituting those homozygous for inactive alleles and therefore having no CYP2C19 activity, occurs with a frequency of 2.5 to 6% in Caucasians. Higher frequencies are observed in Chinese (15-17%) and Japanese (18 -23%) populations (Inaba et al, 1984;Wedlund et al, 1984;Jurima et al, 1985;Nakamura et al, 1985;Horai et al, 1989;Bertilsson et al, 1992). PMs may be more likely to experience adverse drug effects due to increased plasma concentration and/or increased half-life of the parent drug.…”