Gastroenteroloji Alanında Farmakogenetik Bilginin Kullanılması

İlaçlara karşı elde edilen yanıtların bireyler veya etnik gruplar arasındaki farklılıklarının nedenini açıklayan araştırma alanı farmakogenetik bilimidir. Genetik farklılıklar nedeniyle ilaçlardan istenen yanıt elde edilemeyeceği gibi, bir takım yan etkiler de ortaya çıkabilir. Hekim olarak en çok arzu ettiğimiz konuların başında, hastamızın doğru ilaçla, doğru sürede tedavisinin gerçekleşmesini sağlamak gelmektedir. Fakat bu her zaman mümkün olmamaktadır. Bu başarısızlığın en önemli sebeplerinden biri de ilaçların metabolizmasında rol alan sitokrom P450 (CYP) enzimlerindeki genetik değişikliklerdir. Dolayısıyla hastalara uygulayacağımız ilaçların hangi enzimler aracılığı ile metabolize edildiğini ve hastaların genetik özelliklerini bilmek önem kazanmaktadır. Bu makalede özellikle gastroenteroloji alanında kullanılan proton pompa inhibitörlerinin CYP2C19 gen polimorfizminden nasıl etkilendiği ve klinik yansımaları tartışılmıştır

The Use of Pharmacogenetic Knowledge in Gastroenterology

Pharmacogenetic is the science explaining inter-individual variability and variability among ethnic groups for drug responses and the related reasons. Genetic variances might lead side effects besides improper drug response or failed treatment. All clinicians aim to apply correct treatment to patients using correct medication for proper period. However this is not always possible. This failure may be mostly caused by genetic variations in P450(CYP) that coordinates the metabolism of drug. Therefore, enzymes that play role in the metabolism of drugs applied to patients and genetic variations of the patients should be known. In this paper, we aimed to discuss how the proton pump inhibitors are affected by CYP2C19 gene-polymorphisims and its clinical aspects

PDF

___

Vakil N, Megraud F. Eradication therapy for Helicobacter pylori. Gastroenterology 2007;133(3):985-1001.
Smalley WE, Griffin MR. The risks and costs of upper gastrointestinal disease attributable to NSAIDs. Gastroenterol Clin North Am 1996;25(2):373-96.
Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002;347(15):1175-86.
Forman D. Helicobacter pylori and gastric cancer. Scand J Gastroenterol Suppl 1996; 220:23-6.
Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983;1(8336):1273-5.
O'Connor A, Molina-Infante J, Gisbert JP, O'Morain C. Treatment of Helicobacter pylori infection 2013. Helicobacter 2013;18(1):58-65.
Dixon MF. Pathology of Gastritis and Peptic Ulceration. in Helicobacter pylori: Physiology and Genetic. Mobley HLT, Mendz GL, Hazell SL (Editors),Washington (DC): ACM Press; 2001.
Baron JH. The history of acid inhibition. Yale J Biol Med 1994;67(3-4):97-106.
Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil 2013;19(1):25-35.
Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep 2008;10(6):528-34.
Özden A. Hp'nin 30. Yılı (1983-2013) Helicobacter pylori Eradikasyonunda Proton Pompa İnhibitörlerinin Yarattığı Mucize Güncel Gastroenteroloji 2013; 17(2): 119-131.
Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279(15):1200-5.
Kirchheiner J, Seeringer A. Clinical implications of pharmacogenetics of cytochrome P450 drug metabolizing enzymes. Biochim Biophys Acta 2007;1770(3):489-94.
Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet 2009;48(11):689-723.
Klotz U. The role of pharmacogenetics in the metabolism of antiepileptic drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet 2007; 46(4): 271-9.
Shi S, Klotz U. Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol 2008;64(10):935-51.
Goldstein JA. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol 2001;52(4):349-55.
Hunfeld NG, Mathot RA, Touw DJ, van Schaik RH, Mulder PG, Franck PF, et al. Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol 2008;65(5):752-60.
Kodaira C, Sugimoto M, Nishino M, Yamade M, Shirai N, Uchida S, et al. Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects. Eur J Clin Pharmacol 2009;65(6):593-600.
Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ. Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 1979;16(3):183-7.
Kupfer A, Preisig R. Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol 1984;26(6):753-9.
Ward SA, Goto F, Nakamura K, Jacqz E, Wilkinson GR, Branch RA. S-mephenytoin 4- hydroxylase is inherited as an autosomal-recessive trait in Japanese families. Clin Pharmacol Ther 1987;42(1):96-9.
Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, et al. Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans. Biochemistry 1994;33(7):1743-52.
Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA. Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. Biochemistry 1991;30(13):3247-55.
Wedlund PJ. The CYP2C19 enzyme polymorphism. Pharmacology 2000; 61(3): 174-83.
Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, et al. Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther 1998;286(3):1490-5.
Hu LM, Dai DP, Hu GX, et al. Genetic polymorphisms and novel allelic variants of CYP2C19 in the Chinese Han population. Pharmacogenomics 2012;13(14):1571-81.
Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 2006;79(1):103-13.
Sibbing D, Koch W, Gebhard D, Schuster T, Braun S, Stegherr J, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 2010;121(4):512-8.
Gumus E, Karaca O, Babaoglu MO, et al. Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype-phenotype correlation in childhood. Eur J Clin Pharmacol 2012;68(5):629-36.
Hirota T, Eguchi S, Ieiri I. Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of clinically used drugs. Drug Metab Pharmacokinet 2013;28(1):28-37.
Aynacioglu AS, Sachse C, Bozkurt A, Kortunay S, Nacak M, Schroder T, et al. Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population. Clin Pharmacol Ther 1999;66(2):185-92.
Rosemary J, Adithan C. The pharmacogenetics of CYP2C9 and CYP2C19: ethnic variation and clinical significance. Curr Clin Pharmacol 2007; 2(1): 93-109.
Furuta T, Shirai N, Sugimoto M, Ohashi K, Ishizaki T. Pharmacogenomics of proton pump inhibitors. Pharmacogenomics 2004;5(2):181-202.
Kurzawski M, Gawronska-Szklarz B, Wrzesniewska J, Siuda A, Starzynska T, Drozdzik M. Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients. Eur J Clin Pharmacol 2006;62(10):877-80.
Klotz U. Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. Int J Clin Pharmacol Ther 2006;44(7):297-302.
Shirai N, Furuta T, Xiao F, et al. Comparison of lansoprazole and famotidine for gastric acid inhibition during the daytime and night-time in different CYP2C19 genotype groups. Aliment Pharmacol Ther 2002;16(4):837-46.
Saitoh T, Otsuka H, Kawasaki T, et al. Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during proton pump inhibitor maintenance therapy. Hepatogastroenterology 2009;56(91-92):703-6.
Furuta T, Shirai N, Watanabe F, et al. Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther 2002;72(4):453-60.
Sugimoto M, Furuta T, Shirai N, et al. Different dosage regimens of rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotype status. Clin Pharmacol Ther 2004;76(4):290-301.