The clinical relevance of CYP2C19 genotype status on the rational drug treatment

CYP2C19基因多态性已被确认。据报道，CYP2C19代谢不良者（PM）的发生率在种族间存在显著差异；高加索人占2-4%，日本人占15-20%。质子泵抑制剂（PPI），如奥美拉唑（OPZ），已广泛应用于上胃十二指肠疾病，主要由CYP2C19代谢。因此，本研究的目的是研究CYP2C19基因型状态与根除幽门螺杆菌治疗的临床相关性。研究1：记录15名健康志愿者在服用20mg奥美拉唑或安慰剂后24小时的胃内pH值。在给药后24小时内测定奥美拉唑及其2种代谢物和胃泌素的血浆水平。奥美拉唑给药后，三组（homEM、hetEM、PM）胃内平均pH值和胃泌素、奥美拉唑及其代谢物的血浆水平均有显著差异，而安慰剂组在这些参数上无显著差异。研究2:62例消化性溃疡合并幽门螺杆菌感染患者给予奥美拉唑20 mg / d +阿莫西林500 mg / d双重治疗，疗程2周。双重治疗1个月后，根据病史、快速脲酶试验、培养、PCR和13c -尿素呼气试验评估幽门螺杆菌感染的治愈情况。62例患者中32例（51.6%）幽门螺杆菌感染治愈。幽门螺杆菌感染的治愈率明显依赖于CYP2C19基因型状态：homEM、hetEM和PM组分别为28.6%、60.0%和100%。CYP2C19基因分型检测有助于幽门螺杆菌的合理根除治疗。

The genetic polymorphism of CYP2C19 has been recognized. The marked interethnic differences in the incidence of poor metabolizers (PM) of CYP2C19 have been reported ; 2-4% in Caucaisian, 15-20% in Japanese. Proton pump Inhibiter (PPI) such us omeprazole (OPZ), which have been widely used in the upper gastroduodenal diseases, is mainly metabolized by CYP2C19. Therefore, the aim of this study is to examine the clinical relevance of CYP2C19 genotype status on the eradication therapy of H.pylori.Study 1 : Intragastric pH values were recorded for 24 hours in 15 healthy volunteers after a 20 mg of omeprazole or a placebo. Plasma levels of omeprazole and its 2 metabolites and gastrin were measured throughout 24 hours after administration. After omeprazole administration, significant differences in mean intragastric pH values and plasma levels of gastrin, omeprazole and its metabolites were observed among the 3 groups (homEM, hetEM, PM), whereas no significant differences in these parameters were observed with the placebo.Study 2 : Sixty two patients with peptic ulcer and H.pylori infection underwent the dual therapy with 20 mg of omeprazole once a day and 500 mg of amoxicillin qid for 2 weeks. At one month after the dual treatment, cure of H.pylori infection was assessed on the basis of history, a rapid urease test, culture, PCR and 13C-urea breath test. Cure of H.pylori infection was achieved in 32 of the 62 patients (51.6%). Cure rates for H.pylori infection were clearly dependent on CYP2C19 genotype status : homEM, hetEM, and PM groups were 28.6%, 60.0%, and 100%, respectively.The genotyping test for CYP2C19 is useful for the rational eradication therapy of H.pylori.