Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients
- 440 Downloads
To investigate the impact of CYP2C19 genotype on serum concentrations of sertraline and N-desmethyl sertraline in psychiatric patients.
Patients treated with sertraline (n = 121) were divided into six subgroups according to CYP2C19 genotype: CYP2C19*17/*17, CYP2C19*1/*17, CYP2C19*1/*1, CYP2C19*17/def, CYP2C19*1/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 CYP2C19*1/*1 subgroup as reference.
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 CYP2C19*1/*1 subgroup (P < 0.01). The CYP2C19*17 allele had no influence on the dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline.
The significantly higher serum concentrations associated with alleles encoding defective CYP2C19 metabolism might be of relevance for the clinical outcome of sertraline treatment.
KeywordsCYP2C19 CYP2C19*17 Genotype Sertraline N-desmethyl sertraline
The authors thank Marianne Hjerpset, Lene Kristin Støten and Linda Uthus for performing the serum analyses and the genotyping.
- 4.Human Cytochrome P450 Allele Nomenclature Committee CYP2C19 allele nomenclature. http://www.cypalleles.ki.se/cyp2C19.htm Accessed May 2008
- 17.Norwegian Institute of Public Health, Department of Pharmacoepidemiology (2008) Drug Consumption in Norway 2003–2007. http://www.legemiddelforbruk.no/english/. Accessed May 2008
- 25.Indiana University School of Medicine (2008) Drug interactions. Cytochrome P450 system. http://medicine.iupui.edu/flockhart/. Accessed Feb 2008
- 26.www.cyp450.no (2008) Cytochrome P450. www.CYP450.no. Accessed Feb 2008
- 29.Altman DG (1999) Practical statistics for medical research. Chapman & Hall/CRC, Boca Raton, pp 229–276Google Scholar