CYP3A4、PXR和IL-10基因多态性对43名中国健康受试者空腹及餐后口服氨氯地平药代动力学特征的影响

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摘要目的考察细胞色素P450 3A4（CYP3A4）、孕烷X 受体（PXR）和白介素-10（IL-10）的基因多态性对氨氯地平在43 名中国健康受试者体内药代动力学过程的影响。方法本临床研究完成于2015年，并获得了医学伦理委员会的批准，招募43 名男性受试者，对其CYP3A4（17776 A insertion、15820C>G、13989A>G）、PXR（24381A>C、3'UTR11193T>C、3'UTR10719G>A）、IL-10（1082G>A、819C>T、592C>A）9 个突变点予以限制性片段长度多态性聚合酶链反应（PCR-RELP）方法进行基因分析，受试者口服10 mg 氨氯地平后体内氨氯地平的血药浓度通过已建立并进行方法学确证的液相二级质谱（LC-MS/MS）方法测定获得。结果 3 个CYP3A4 基因型、3 个PXR 基因型和3 个IL-10 基因型对氨氯地平在体内的药动学参数无明显影响（P＞0.05）。餐后组氨氯地平的峰浓度（cmax）、药时曲线下面积（AUC0-t）和AUC0-∞高于空腹组，差异有统计学意义（P＜0.05）。结论 CYP3A4、PXR 和IL-10 基因多态性对氨氯地平在43 名中国健康受试者体内药代动力学过程无明显影响，而高脂高热量饮食会明显促进氨氯地平在人体的吸收。

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	刘林林
	阿萨亚
	刘建芳
	陈琳
	刘丹
	谢宏波
	刘名义
	夏春华

关键词 ：细胞色素P450 3A4, 白介素-10, 孕烷X 受体, 基因多态性, 氨氯地平, 药代动力学

Abstract：Objective To investigate the effect of gene polymorphisms of cytochrome P450 3A4 (CYP3A4), pregnane X receptor (PXR) and interleukin-10 (IL-10) on the pharmacokinetics of amlodipine in 43 healthy Chinese subjects.Methods Genetic polymorphisms of CYP3A4, PXR, and IL-10 were evaluated for 43 healthy Chinese male subjects from a study permitted by ethical committee of the hospital and finalized in 2015. CYP3A4 genotype in 17776 A insertion, 15820C>G, 13989A>G, and PXR genotype in 24381A>C, 3'UTR11193T>C, 3'UTR10719G>A, and IL-10 genotype in 1082G>A, 819C>T and 592C>A were assessed by PCR–RFLP assays. The plasma concentrations of amlodipine in subjects after being orally administrated 10 mg Amlodipine were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Results Three CYP3A4 genotypes, three PXR genotypes and three IL-10 genotypes had no significant effect on the pharmacokinetic parameters of amlodipine in vivo (P＞0.05). The peak concentration (cmax), area under the curve (AUC0-t) and AUC0-∞of amlodipine in postprandial group were higher than those in fasting group, and the differences were statistically significant (P＜0.05). Conclusion There are no influences of the genetic polymorphisms of CYP3A4, PXR, IL-10 on the pharmacokinetics of Amlodipine in Chinese healthy subjects.And the high-fat and high-calorie diet could significantly promote the absorption of Amlodipine in human.

Key words： Cytochrome P450 3A4 Interleukin -10;Pregnane X receptor Gene polymorphism Amlodipine;Pharmacokinetics

基金资助:国家科技重大专项课题（2020ZX09201-027）。

通讯作者: 夏春华（1972-），男，江西丰城人，博士，二级教授，研究方向：临床药理学。

作者简介: 刘林林（1974-），女，江西龙南人，硕士，副主任药师，研究方向：临床药理学

引用本文:

刘林林；阿萨亚；刘建芳；陈琳；刘丹；谢宏波；刘名义；夏春华. CYP3A4、PXR和IL-10基因多态性对43名中国健康受试者空腹及餐后口服氨氯地平药代动力学特征的影响[J]. 中国当代医药, 2021, 28(30): 4-7转12.
LIU Lin-lin；IsaiahTakau；LIU Jian-fang； CHEN Lin；LIU Dan； XIE Hong-bo； LIU Ming-yi； XIA Chun-hua. Effect of CYP3A4, PXR and IL-10 polymorphisms on the pharmacokinetics of Amlodipine in 43 healthy Chinese subjects before and after meal. 中国当代医药, 2021, 28(30): 4-7转12.

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http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2021/V28/I30/4

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