细胞色素P4502C9与通道亚家族J成员11基因多态性对中国健康受试者单剂量口服格列喹酮的药代动力学影响  

Influence of cytochrome P4502C9 and rectifying channel subfamily J,member 11 gene polymorphisms on the pharmacokinetics of single dose oral gliquidone in healthy Chinese subjects

作　　者：周双[1,3] 解染 张晓丹[1] 何旭[1] 赵彩芸[2] 吕媛[2] 高倩 刘茜英 赵侠[1] 崔一民[1,2,3] ZHOU Shuang;XIE Ran;ZHANG Xiao-dan;HE Xu;ZHAO Cai-yun;LÜ Yuan;GAO Qian;LIU Qian-ying;ZHAO Xia;CUI Yi-min(Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China;Administration and Clinical Pharmacy School of Pharmaceutical Science,Department of Pharmacy,Peking University Beijing 100191,China;China Resources Double-Crane Pharmaceutical Co.,Ltd,Beijing 100102,China)

机构地区：[1]北京大学第一医院,药学部,北京100034 [2]北京大学第一医院,临床药理研究所,北京100034 [3]北京大学药学院药事管理与临床药学系,北京100191 [4]华润双鹤药业股份有限公司,北京100102

出　　处：《中国临床药理学杂志》2022年第23期2874-2878,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项-重大新药创制课题资助项目(2017ZX09101001);医药创新品种研发培育及产业支撑平台能力建设课题资助项目(Z191100007619038)。

摘　　要：目的探讨中国健康受试者细胞色素P4502C9(CYP2C9)和通道亚家族J成员11基因(KCNJ11)基因多态性对格列喹酮药代动力学(PK)的影响。方法将48例中国健康受试者,单次给予格列喹酮片30 mg,用液相色谱串联质谱法测定格列喹酮血样浓度,计算PK参数,比较不同基因型对C_(max)、AUC_(0-t)、AUC_(0-∞)、t_(max)和t_(1/2)的影响。结果口服格列喹酮片后,CYP2C9*3为AA和AC基因型的C_(max)分别为(482.02±166.28)和(821.83±255.92)ng·mL^(-1),t_(1/2)分别为(9.90±4.27)和(5.21±1.17)h,AUC_(0-t)分别为(3053.76±816.14)和(4985.33±1206.58)ng·mL^(-1)·h,AUC_(0-∞)分别为(3284.07±790.12)和(5103.83±1223.00)ng·mL^(-1)·h。与CYP2C9*3 AA基因型相比,携带AC基因型受试者的C_(max)、t_(1/2)、AUC_(0-t)和AUC_(0-∞)差异均有统计学意义(P<0.01,P<0.001),对于t_(max)的影响差异无统计学意义(P>0.05)。CYP2C9*27(rs7900194)和KCNJ11(rs5219)不同基因型间,主要PK参数差异均无统计学(均P>0.05)。结论CYP2C9*3基因多态性可能影响格列喹酮的代谢。在应用格列喹酮时,应充分考虑CYP2C9基因多态性的影响,实现临床个体化精准用药,以保障临床用药的疗效及安全。Objective To investigate the effects of cytochrome P4502C9(cytochrome P4502C9,CYP2C9)and rectifying channel subfamily J,member 11(KCNJ11)polymorphisms on the pharmacokinetics of gliquidone in healthy Chinese subjects.Methods A total of 48 healthy Chinese subjects were given a single dose of 30 mg of glazoquinone tablets.The blood concentration of glazoquinone was determined by liquid chromatography tandem mass spectrometry.Pharmacokinetic parameters were calculated.Results After oral administration of glazoquinone,the C_(max)of CYP2C9*3 AA and AC genotypes were(482.02±166.28)and(821.83±255.92)ng·mL^(-1),t_(1/2)were(9.90±4.27)and(5.21±1.17)h,AUC_(0-t)were(3053.76±816.14)and(4985.33±1206.58)ng·mL^(-1)·h,AUC_(0-∞)were(3284.07±790.12)and(5103.83±1223.00)ng·mL^(-1)·h,respectively.Compared with CYP2C9*3 AA,the pharmacokinetic parameters of gliquidone in AC genotype subjects were statistically different in C_(max),t_(1/2),AUC_(0-t)and AUC_(0-∞)(P<0.01,P<0.001),but not in t_(max)(P>0.05).There were no statistically significant differences in major pharmacokinetic parameters between the two groups with different CYP2C9*27(rs7900194)and KCNJ11(rs5219)genotypes(all P>0.05).Conclusion The CYP2C9*3 gene polymorphism may affect the metabolism of gliquidone,and it is recommended that the CYP2C9 gene polymorphism should be taken into consideration prior to the use of gliquidone in order to achieve individualized clinical use and safety.

关 键 词：格列喹酮 细胞色素P4502C9 药代动力学 基因多态性 

分 类 号：R977.15[医药卫生—药品]