Venlafaxine Metabolism as a Marker of Cytochrome P450 Enzyme 2D6 Metabolizer Status

被引:44
作者
Nichols, Alice I. [1 ]
Lobello, Kasia [1 ]
Guico-Pabia, Christine J. [1 ]
Paul, Jeff [1 ]
Preskorn, Sheldon H. [2 ,3 ]
机构
[1] Wyeth Res, Collegeville, PA 19426 USA
[2] Univ Kansas, Sch Med, Dept Psychiat, Wichita, KS 67214 USA
[3] Univ Kansas, Sch Med, Clin Res Inst, Wichita, KS 67214 USA
关键词
CYP2D6; poor metabolizers; extensive metabolizers; O-desmethylvenlafaxine; venlafaxine; CYP2D6; GENOTYPE; IN-VITRO; PHARMACOKINETICS; DEBRISOQUINE; OXIDATION; ANTIDEPRESSANTS; DEMETHYLATION; HYDROXYLATION; POLYMORPHISM;
D O I
10.1097/JCP.0b013e3181acc4dd
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: One of the major enzymes of the cytochrome P450 drug-metabolizing system, CYP2D6, shows a high degree of genetic polymorphism and variability in activity. Based on the degree of CYP2D6 activity, individuals can be broadly classified as poor metabolizers (PMs) or extensive metabolizers (EMs); the metabolism of CYP2D6 substrates differs among PMs and EMs. The metabolism of various drugs that are substrates of CYP2D6 has been used as a marker for metabolic phenotype, calculating the plasma or urinary metabolic ratio of the parent compound to its metabolite. The current analysis evaluates the use of the O-desmethylvenlafaxine-venlafaxine ratio (ODV/VEN) after administration of VEN, a CYP2D6 substrate, for determining CYP2D6 metabolic phenotype in healthy adults receiving VEN. Methods: The analysis included data from 2 studies in which healthy adults were classified as either EMs or PMs using established methods (I genotypic and 1 phenotypic) and were then administered VEN at daily dosages ranging from 75 to 150 mg. Blood plasma samples were taken at various time points, and the ODV/VEN ratio was calculated. Results: Blood samples from 28 participants in the 2 studies were available for analysis. The ODV/VEN ratio distinguished the EM and PM phenotypes; ratios were I or greater for EMs and less than I for PMs at 4 hours after dose administration. Conclusions: The ratio of ODV/VEN is an effective means of phenotyping individuals according to their CYP2D6 metabolizer status.
引用
收藏
页码:383 / 386
页数:4
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