Impact of Genetic Polymorphisms in CYP2C9 and CYP2C19 on the Pharmacokinetics of Clinically Used Drugs

Abstract

Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20% of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CYP2C19 have been reported. The frequencies of these variants show marked inter-ethnic variation. The functional consequences of genetic polymorphisms have been examined, and many studies have shown the clinical importance of these polymorphisms. Current evidence suggests that taking the genetically determined metabolic capacity of CYP2C9 and CYP2C19 into account has the potential to improve individual risk/benefit relationships. However, more prospective studies with clinical endpoints are needed before the paradigm of "personalized medicine" based on the variants can be established. This review summarizes the currently available important information on this topic.

TheCYP2C19Intron 2 Branch Point SNP is the Ancestral Polymorphism Contributing to the Poor Metabolizer Phenotype in Livers withCYP2C19*35andCYP2C19*2Alleles

“…There are numerous reports linking the CYP2C19*2 allele to altered substrate clearance (Hicks et al, 2013;Hirota et al, 2013;Owusu Obeng et al, 2014). Over 34 CYP2C19 variant alleles have been identified in a CYP database (http://www.cypalleles.ki.se/cyp2c19.…”

Metabolic Profiling of the Novel Hypoxia-Inducible Factor 2α Inhibitor PT2385 In Vivo and In Vitro

“…CYP2C19 plays a critical role in the metabolism of drugs, including anticancer, antidepressant, antihypertensive, antiplatelet and antiulcer drugs (Hirota et al, 2013). However, CYP2C19 is polymorphic with 12-23% of null alleles in Asians and 3-5% in Caucasians leading to significant inter-individual differences in activity that could result in different metabolism rates and fluctuations in exposure levels of PT2385 (Goldstein and de Morais, 1994;Umamaheswaran et al, 2014).…”

Gastroenteroloji Alanında Farmakogenetik Bilginin Kullanılması

“…Ülkemizinde içinde bulunduğu beyaz ırkta YM sıklığı %3-5 iken Asyalılarda bu oran %12-23'tür. 30,31 CYP2C19*4: Ekzon 1 üzerinde Adenin yerine Guanin gelmesi sonucu ortaya çıkar. Bu değişim sonucu enzim sentezi yeterli oranda gerçekleşmez.…”