The impact of CYP2C19 polymorphisms on citalopram metabolism in patients with major depressive disorder

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dc.contributor.authorUçkun, Zuhal
dc.contributor.authorBaşkak, Bora
dc.contributor.authorÖzel-Kızıl, Erguvan Tuğba
dc.contributor.authorÖzdemir, Hatice
dc.contributor.authorÖzgüven, Halise Devrimci
dc.contributor.authorSüzen, Halit Sinan
dc.date.accessioned2020-06-25T18:12:36Z
dc.date.available2020-06-25T18:12:36Z
dc.date.issued2015
dc.departmentKırıkkale Üniversitesi
dc.descriptionSuzen, Sinan/0000-0003-1779-5850; OZEL-KIZIL, ERGUVAN TUGBA/0000-0001-9657-1382; ozguven, halise/0000-0002-9355-2757
dc.description.abstractWhat is known and objective: Genetic variations in drug-metabolizing enzyme genes change drug pharmacokinetics and response. CYP2C19 is a clinically important enzyme that metabolizes citalopram (CIT). The objective of this study was to determine CYP2C19 genetic polymorphisms and to evaluate the impact of these polymorphisms on the metabolism of citalopram in a sample of the Turkish population. We also assessed *17 polymorphism in healthy subjects in this population. Methods: The CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (209 healthy individuals and 50 patients for CIT metabolism), and the plasma concentrations of CIT and demethylcitalopram (DCIT) were quantified by high-performance liquid chromatography. Results and discussion: The CYP2C19*1 and *17 allele frequencies for the patient group and the healthy group were 71.0%, 18.0% and 81.1%, 18.9%, respectively. There was no significant difference between the two groups (P > 0 . 05). The mean plasma concentrations and the mean dose-corrected (C/D) plasma levels of DCIT were significantly higher in patients with the CYP2C19*1/*1 genotype compared to patients with CYP2C19*1/*2 and CYP2C19*2/*2 genotypes (P < 0 . 05). Furthermore, the mean metabolic ratio (MR, CIT/DCIT) was also significantly higher in the CYP2C19*1/*2 + CYP2C19*2/*2 genotypes (P < 0 . 05). On the other hand, plasma CIT, DCIT concentrations and M/R value in the CYP2C19*1/*1 genotypes were no different to those of the CYP2C19*1/*17 genotypes (P > 0 . 05). What is new and conclusion: Our data suggest that CYP2C19*17 polymorphism does not have a significant effect on CIT metabolism. 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.en_US
dc.description.sponsorshipScientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S147]en_US
dc.description.sponsorshipThis work was supported by The Scientific and Technological Research Council of Turkey under Project 109S147.en_US
dc.identifier.citationclosedAccessen_US
dc.identifier.doi10.1111/jcpt.12320
dc.identifier.endpage679en_US
dc.identifier.issn0269-4727
dc.identifier.issn1365-2710
dc.identifier.issue6en_US
dc.identifier.pmid26343256
dc.identifier.scopus2-s2.0-84983134902
dc.identifier.scopusqualityQ2
dc.identifier.startpage672en_US
dc.identifier.urihttps://doi.org/10.1111/jcpt.12320
dc.identifier.urihttps://hdl.handle.net/20.500.12587/5980
dc.identifier.volume40en_US
dc.identifier.wosWOS:000368268000010
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWileyen_US
dc.relation.ispartofJournal Of Clinical Pharmacy And Therapeutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectcitalopramen_US
dc.subjectCYP2C19en_US
dc.subjectgenetic polymorphismsen_US
dc.subjectmajor depressive disorderen_US
dc.titleThe impact of CYP2C19 polymorphisms on citalopram metabolism in patients with major depressive disorderen_US
dc.typeArticle

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