Klin Farmakol Farm. 2012;26(2):90-92

Venlafaxine intoxication - importance of TDM, phenotyping and genotyping

Milan Grundmann¹, Romana Uřinovská², Petr Šilhán³, Ivana Kacířová^1,2

¹ Ústav klinické farmakologie, Lékařská fakulta Ostravské univerzity, Ostrava

² Oddělení klinické farmakologie, Fakultní nemocnice Ostrava

³ Oddělení psychiatrické, Fakultní nemocnice Ostrava

Introduction: Antidepressive drug venlafaxine belongs to the serotonine and norepinephrine reuptake inhibitors. It is primary metabolized

by CYP2D6 to its active metabolite O-desmethylvenlafaxine and by CYP3A4 to N-desmethylvenlafaxine. The range 0.3–5.2 for

O-desmethylvenlafaxine/venlafaxine ratio was estimated for extensive and intermediate metabolizers.

Method: There is described intoxication of woman (41 years) treated by combination therapy venlafaxine 150 mg/day, mianserine 60 mg/

day, clonazepam 1 mg/day and olanzapine 10 mg/day. Patient was administered at home an indefinite amount of these psychofarmacs.

TDM of these substances was provided using LC-MS/MS method to estimate phenotype of venlafaxine and to compare with genotype.

Results: On admission toxic plasma level of venlafaxine was found (2 638 ng/mL) and after reduction of the dose to 75 mg/day plasma

level was estimated in therapeutic range. The ratio O-desmethylvenlafaxine/venlafaxine was estimated between 0.005 and 0.016 showing

poor metabolizer. Genetic examination detected homozygotes deletion of the gene CYP2D6 *5/*5 and explained phenotype.

Conclusion: The ratio of the metabolite to the parent substance (phenotype) allows us to detect any deviation in the metabolism of drugs

which can be subsequently explained by determination of genotype. Therapeutic drug monitoring contributes to the optimalization of

pharmacotherapy in the case of psychotropic drugs.

Keywords: venlafaxine, intoxication, TDM, phenotype, genotype

Published: July 31, 2012  Show citation