6533b837fe1ef96bd12a331a

RESEARCH PRODUCT

Severe Tremor After Cotrimoxazole-Induced Elevation of Venlafaxine Serum Concentrations in a Patient With Major Depressive Disorder

Christian GeberElnaz Ostad HajiKonrad F SchlichtAndré TadićChristoph Hiemke

subject

medicine.medical_specialtyCYP2D6Venlafaxine HydrochlorideVenlafaxineCYP2C19Severity of Illness IndexGastroenterologyAnti-Infective AgentsInternal medicineTremorTrimethoprim Sulfamethoxazole Drug CombinationHumansMedicineDrug InteractionsPharmacology (medical)PsychiatryCYP2C9PharmacologyDepressive Disorder MajorCYP3A4business.industryVenlafaxine HydrochlorideMiddle AgedCyclohexanolsmedicine.diseaseTrimethoprimCytochrome P-450 CYP2C19Cytochrome P-450 CYP2D6Major depressive disorderFemaleAryl Hydrocarbon HydroxylasesbusinessSelective Serotonin Reuptake Inhibitorsmedicine.drug

description

: We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 due to a genetic deficit and (2) inhibition of CYP2C9 by cotrimoxazole.

yearjournalcountryeditionlanguage
2013-05-14Therapeutic Drug Monitoring
https://doi.org/10.1097/ftd.0b013e31828816e0