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Effect of the CYP2D6*10
genotype on venlafaxine pharmacokinetics in healthy adult
volunteers.
Fukuda T, Yamamoto I, Nishida Y, Zhou
Q, Ohno M, Takada K, Azuma J.
Department of Pharmacokinetics,
Kyoto Pharmaceutical University, Kyoto, Japan.
AIMS:
Interindividual differences in the pharmacokinetics of venlafaxine, a
new antidepressant, were shown during early clinical trials in Japan.
Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite,
O-desmethylvenlafaxine (ODV). Therefore, the influence of the CYP2D6
genotypes on venlafaxine pharmacokinetics was examined in a Japanese
population. METHODS: Twelve adult Japanese men in good health
participated in this study. Genomic DNA was isolated from peripheral
lymphocytes, and the CYP2D6 genotypes were determined by codon 188C/T,
1934G/A, 2938G/A and 4268G/C mutations using endonuclease tests based on
PCR and by Xba I-RFLP analysis. Subjects were categorized into the
following 3 groups (n=4 in each group); Group1: CYP2D6*10/*10, *5/*10,
Group2: CYP2D6*1/*10, *2/*10 and Group3: CYP2D6*1/*1, CYP2D6*1/*2.
Venlafaxine (25 mg, n=6; 37.5 mg, n=6) was administered orally at 09.00
h following an overnight fast. Plasma concentrations of venlafaxine and
ODV were monitored by h.p.l.c. for 48 h. RESULTS: The Cmax and AUC of
venlafaxine were 184% and 484% higher in the group 1 subjects than in
the group 3 subjects, and 101% and 203% higher in the group 1 than in
the group 2, respectively. CONCLUSIONS: These results suggest that
CYP2D6*10 influences the pharmacokinetics of venlafaxine in a Japanese
population.
PMID: 10233212 [PubMed - indexed for MEDLINE]
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