CYP2C19 polymorphisms impacts citalopram metabolism

(HealthDay)—For patients with major depressive disorder, certain CYP2C19 polymorphisms contribute to citalopram (CIT) metabolism, according to research published in the December issue of the Journal of Clinical Pharmacy and Therapeutics.

Z. Uckun, Ph.D., from Mersin University in Turkey, and colleagues determined CYP2C19 genetic polymorphisms and their impact on the metabolism of CIT. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method in 209 healthy individuals and 50 patients with major depressive disorder.

The researchers found that the CYP2C19*1 and CYP2C19*17 allele frequencies were 71.0 and 18.0 percent, respectively, for the healthy group and 81.1 and 18.9 percent, respectively, for the patient group (P > 0.05). Patients with the CYP2C19*1/*1 genotype had significantly higher mean plasma concentration and the mean dose-corrected plasma levels of demethylcitalopram (DCIT) compared to patients with CYP2C19*1/*2 or CYP2C19*2/*2 genotypes (P < 0.05). In the CYP2C19*1/*2 and CYP2C19*2/*2 genotypes, the mean metabolic ratio (MR, CIT/DCIT) was significantly higher (P < 0.05). Plasma CIT, DCIT concentrations, and MR value did not differ for the CYP2C19*1/*1 and CYP2C19*1/*17 genotypes (P > 0.05).

"Our data suggest that CYP2C19*17 polymorphism does not have a significant effect on CIT metabolism," the authors write. "In contrast CYP2C19*2 polymorphism has a prominent role and is likely to contribute to interindividual variability in CIT metabolism in vivo at therapeutic doses."