Major depresyon hastalarında Sitalopramın farmakogenetik ve farmakokinetik yönünden araştırılması
Abstract
The aim of this study is to investigate citalopram in point of pharmacogenetic and pharmacokinetic in patients with major depression. For this reason, polymorphisms in genes affecting (CYP2C19*2, CYP2C19*17, CYP3A4*1B) pharmacokinetic and pharmacodinamic (SERT L/S, BDNF Val66Met) of citalopram have been investigated. The polymorphisms in those genes were determined by using polimerase chain reaction and restriction fragment length polymorphism. Plasma concentrations of citalopram and its major metabolite desmethycitalopram were measured by using high performance liquid chromatography.Interindividual variations in plasma concentrations of citalopram was not statistically difference in terms of CYP2C19*2 allel (p>0,05). However, there were statistically significant differences in desmethycitalopram plasma concentration and in citalopram to desmethycitalopram or desmethycitalopram to citalopram ratios (CIT-to-DCIT or DCIT-to-CIT ratio) between depressed patients with CYP2C19*1/*2 + *2/*2 and with CYP2C19*1/*1 genotypes (p<0,05). Patients carrying *2 allele had significantly higher CIT to DCIT ratio and lower DCIT plasma concenration than patients carrying wild type. In addition to them, clinical response to citalopram was determined by 17 items HAM-D, side effects were determined by UKU side effects rating scale and severity of illness was observed by CGI. We observed that there was no statistically significant difference between response and non-response patients in terms of citalopram and desmethycitalopram plasma concentrations, CIT-to-DCIT or DCIT-to-CIT ratio, and C/D ratio. However, we had predictive information that patients carrying L and Met alleles had better response than patients carrying other alleles. Besides, we found that there was statistically significant difference in terms of CIT-to-DCIT ratio between patients with and without sexual dysfunction (respectively, 4,32 ± 1,26; 3,24 ± 0,89; in other words, there was 25 % decline or vice versa) (p=0,026). According to the evaluation of UKU side effects scale and CGI-Severity with OR values, patients carrying L allele or LL genotype had higher possibility to seen psychic and other side effects (but not autonomic side effects) and increase severity of illness.Interindividual differences in drug response and side effects cause various problems of efficacy and safety in a considerable number of medicine therapy. Combination of genotyping and therapeutic drug monitoring has a prominent potential of increasing therapeutic efficiency and reducing advers drug reactions, especially in psychopharmacotherapy.