title: Severe tremor after cotrimoxazole-induced elevation of venlafaxine serum concentrations in a patient with major depressive disorder.
abstract: : 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.
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. geber@uni-mainz.de
authors.forename: Christian
authors.initials: C
authors.lastname: Geber
authors.forename: Elnaz
authors.initials: E
authors.lastname: Ostad Haji
authors.forename: Konrad
authors.initials: K
authors.lastname: Schlicht
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.forename: André
authors.initials: A
authors.lastname: Tadić
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D003511:Cyclohexanols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012720:Severity of Illness Index; D014202:Tremor / Q000139:chemically induced*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
chemical_list: D000890:Anti-Infective Agents; D001189:Aryl Hydrocarbon Hydroxylases; D003511:Cyclohexanols; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D017367:Selective Serotonin Reuptake Inhibitors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000069470:Venlafaxine Hydrochloride; C045793:CYP2C19 protein, human