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.
MeSH terms
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Anti-Infective Agents / adverse effects
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Anti-Infective Agents / pharmacology
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Aryl Hydrocarbon Hydroxylases / genetics
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Cyclohexanols / adverse effects
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Cyclohexanols / pharmacokinetics*
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Cyclohexanols / therapeutic use
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Cytochrome P-450 CYP2C19
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Cytochrome P-450 CYP2D6 / genetics
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Depressive Disorder, Major / drug therapy
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Drug Interactions
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Female
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Humans
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Middle Aged
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Selective Serotonin Reuptake Inhibitors / adverse effects
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Selective Serotonin Reuptake Inhibitors / pharmacokinetics*
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Selective Serotonin Reuptake Inhibitors / therapeutic use
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Severity of Illness Index
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Tremor / chemically induced*
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Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
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Trimethoprim, Sulfamethoxazole Drug Combination / pharmacology*
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Venlafaxine Hydrochloride
Substances
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Anti-Infective Agents
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Cyclohexanols
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Serotonin Uptake Inhibitors
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Venlafaxine Hydrochloride
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Trimethoprim, Sulfamethoxazole Drug Combination
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Aryl Hydrocarbon Hydroxylases
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CYP2C19 protein, human
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Cytochrome P-450 CYP2C19
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Cytochrome P-450 CYP2D6