Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients.

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Yuce-Artun N, Baskak B, Ozel-Kizil ET, Ozdemir H, Uckun Z, Devrimci-Ozguven H, Suzen HS

Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients.

Int J Clin Pharm. 2016 Apr;38(2):388-94. doi: 10.1007/s11096-016-0259-8. Epub 2016 Jan 30.

PubMed ID

26830411 [ View in PubMed

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Abstract

BACKGROUND: Genetic polymorphisms in CYP2B6 and CYP2C19 may cause variability in the metabolism of sertraline, a widely used antidepressant in major depressive disorder treatment. OBJECTIVE: This study investigates the impact of CYP2B6*4 (785A > G), CYP2B6*9 (516G > T), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (685G > A), CYP2C19*17 (-3402C > T) polymorphisms on plasma concentrations of sertraline and N-desmethyl sertraline in major depression patients treated with sertraline [n = 50]. SETTING: Participants were patients who admitted to an adult psychiatry outpatient unit at a university hospital. These were DSM-IV major depression diagnosed patients with a stable sertraline medication regimen [for at least one month]. METHODS: CYP2B6*4 (rs 2279343; 785A > G), CYP2B6*9 (516G > T; rs 3745274), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (rs 4244285; 685G > A), CYP2C19*17 (rs 11188072; -3402C > T), polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Plasma concentrations were measured by high-performance liquid chromatography in patients treated with SERT. MAIN OUTCOME MEASURE: The distribution of CYP2B6*4, *6, *9 and CYP2C19*2, *17 among patient group and the association between genotype and sertraline metabolism. RESULTS: Sertraline, N-desmethyl sertraline, N-desmethyl sertraline/sertraline and dose-adjusted plasma concentrations were statistically compared between individuals with wild-type and variant alleles both for CYP2B6 and CYP2C19 enzymes. The mean N-desmethyl sertraline/sertraline value, was significantly lower in all subgroups with *6 and *9 variant alleles (p < 0.05). Sertraline/C values were significantly higher (p < 0.05) and N-desmethyl sertraline/C values were lower in all subgroups with *6 and *9 variant alleles compared to wild-type subgroup. CONCLUSION: CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Sertraline	Cytochrome P450 2B6	Protein	Humans	Unknown	Substrate Inhibitor	Details
Sertraline	Cytochrome P450 2C19	Protein	Humans	Unknown	Substrate Inhibitor	Details