Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients.

OBJECTIVE

To investigate the impact of CYP2C19 genotype on serum concentrations of sertraline and N-desmethyl sertraline in psychiatric patients.

METHODS

Patients treated with sertraline (n = 121) were divided into six subgroups according to CYP2C19 genotype: CYP2C1917/17, CYP2C191/17, CYP2C191/1, CYP2C1917/def, CYP2C191/def and CYP2C19def/def (def = allele encoding defective CYP2C19 metabolism, i.e. *2 and 3). Dose-adjusted serum concentrations were compared by linear mixed model analyses using the CYP2C191/*1 subgroup as reference.

RESULTS

Subgroups carrying one or two alleles encoding defective CYP2C19 metabolism achieved significantly higher mean dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline compared to the CYP2C19*1/1 subgroup (P < 0.05). The effect of CYP2C19 genotype was expressed as 3.2-fold (sertraline) and 4.5-fold (N-desmethyl sertraline) higher dose-adjusted serum concentrations in the CYP2C19def/def subgroup compared to the CYP2C191/1 subgroup (P < 0.01). The CYP2C1917 allele had no influence on the dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline.

CONCLUSION

The significantly higher serum concentrations associated with alleles encoding defective CYP2C19 metabolism might be of relevance for the clinical outcome of sertraline treatment.