Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers
作者： Tsuyoshi Fukuda , Isamu Yamamoto , Yuko Nishida , Qian Zhou , Masako Ohno
DOI: 10.1046/J.1365-2125.1999.00913.X
关键词: Active metabolite 、 Pharmacogenetics 、 Pharmacology 、 Venlafaxine 、 Biology 、 Genotype 、 CYP2D6 、 Cmax 、 Venlafaxine Hydrochloride 、 Pharmacokinetics
摘要: Aims Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV). Therefore, influence genotypes on venlafaxine was examined Japanese population. Methods Twelve adult men good health participated this study. Genomic DNA isolated from peripheral lymphocytes, and determined codon 188C/T, 1934G/A, 2938G/A 4268G/C mutations using endonuclease tests based PCR Xba I-RFLP analysis. Subjects categorized into following 3 groups (n=4 each group); Group1: CYP2D6*10/*10, *5/*10, Group2: CYP2D6*1/*10, *2/*10 Group3: CYP2D6*1/*1, CYP2D6*1/*2. (25 mg, n=6; 37.5 mg, n=6) administered orally at 09.00 h overnight fast. Plasma concentrations ODV monitored by h.p.l.c. for 48 h. Results The Cmax AUC 184% 484% higher group 1 subjects than subjects, 101% 203% 2, respectively. Conclusions These results suggest that CYP2D6*10 influences population.
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