五酯胶囊相较地尔硫?对他克莫司血药浓度的影响与CYP3A5基因多态性的关系

Effect of wuzhi capsules on the blood concentration of tacrolimus relative to diltiazem and CYP3A5 gene polymorphisms

为明确五酯胶囊相较地尔硫[艹卓]对他克莫司血药浓度的影响与细胞色素P450(cytochrom P450,CYP)3A5基因多态性的关系。本研究回顾性收集2014年11月至2018年3月于我院行肾移植术且术后应用他克莫司并联用地尔硫[艹卓](30 mg,bid)的患者病例共计170例,根据患者术后是否换用五酯胶囊(11.25 mg,bid)分为观察组(105例)与对照组(65例),检测患者CYP3A5*3基因多态性,比较不同CYP3A5*3基因型患者五酯胶囊相较地尔硫[艹卓]对他克莫司血药浓度的影响,研究方案均符合相关伦理学规范。结果表明,五酯胶囊相较地尔硫[艹卓]对他克莫司谷浓度/剂量(C0/D)的提升幅度在自身对照及对照组对照中均与患者CYP3A5*3基因型显著相关,观察组患者在由地尔硫[艹卓]换用五酯胶囊后能够提升CYP3A5表达型患者他克莫司C0/D约76.8%,但在CYP3A5非表达型患者中则几乎无这一作用。五酯胶囊较地尔硫[艹卓]在CYP3A5表达型患者中对他克莫司血药浓度的提升作用更强。

To determine the relationship between the effect of wuzhi capsules on the blood concentration of tacrolimus as compared to diltiazem and with regard to cytochrome P450(CYP)3 A5 gene polymorphisms,170 patients who underwent renal transplantation from November 2014 to March 2018 and used tacrolimus combined with diltiazem 30 mg bid were selected in this study retrospectively.Patients were divided into an observation group(105 patients)and a control group(65 patients)according to whether they used wuzhi capsules after the operation.The polymorphisms of CYP3 A5*3 were determined and the effect of wuzhi capsules on the blood concentration of tacrolimus,as compared with that of diltiazem was determined in patients with different CYP3 A5*3 genotypes.This study complies with relevant ethical norms.The results show that compared with diltiazem,an increase of tacrolimus C0/D was significantly correlated with the patient’s CYP3 A5*3 genotype in both the selfcontrol and the control group.CYP3 A5 expressers in the observation group were able to increase the tacrolimus C0/D by about 76.8%by replacing the wuzhi capsules with diltiazem,but this effect was not observed in CYP3 A5 non-expressers.In CYP3 A5 expressers wuzhi capsules had a greater ability relative to diltiazem to increase the blood concentration of tacrolimus.