alexa Venlafaxine serum levels and CYP2D6 genotype.
Microbiology

Microbiology

Journal of Microbial & Biochemical Technology

Author(s): Veefkind AH, Haffmans PM, Hoencamp E

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Abstract Thirty-three patients with depression treated with 225 mg venlafaxine were genotyped for the polymorphic enzyme, debrisoquine 4-hydroxylase (CYP2D6). The relationship between drug and metabolite levels and between genotype and clinical response were investigated. Although the number of responders in this study is insufficient for definite conclusions to be drawn, a target therapeutic concentration ranging from 195-400 microg/L for the sum of venlafaxine and O-desmethylvenlafaxine is suggested. The ratio of O-desmethylvenlafaxine to venlafaxine in the serum concentrations is a measure of metabolic turnover, and can be used to distinguish between ultrarapid and poor metabolizers. All but one of the nonresponders in this study had lower ratios than the responders. Three patients (9\%) had homozygous defective CYP2D6 alleles and did not readily metabolize venlafaxine to O-desmethylvenlafaxine, pointing to poor metabolism. In these patients, N-desmethylation was increased. Two out of four patients detected by the ratio as potentially ultrarapid metabolizers were shown to have multiple copies of a functional CYP2D6 gene.
This article was published in Ther Drug Monit and referenced in Journal of Microbial & Biochemical Technology

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