药学学报, 2020, 55(2): 272-275
引用本文:
蔡宜朋, 陈泉金, 谢培华, 宋洪涛. 五酯胶囊相较地尔硫䓬对他克莫司血药浓度的影响与CYP3A5基因多态性的关系[J]. 药学学报, 2020, 55(2): 272-275.
CAI Yi-peng, CHEN Quan-jin, XIE Pei-hua, SONG Hong-tao. Effect of wuzhi capsules on the blood concentration of tacrolimus relative to diltiazem and CYP3A5 gene polymorphisms[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 272-275.

五酯胶囊相较地尔硫䓬对他克莫司血药浓度的影响与CYP3A5基因多态性的关系
蔡宜朋1,2, 陈泉金2, 谢培华2, 宋洪涛2
1. 福建医科大学附属福州市第一医院药学部, 福建 福州 350009;
2. 中国人民解放军联勤保障部队第九〇〇医院药学科, 福建 福州 350025
摘要:
为明确五酯胶囊相较地尔硫䓬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䓬(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䓬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䓬对他克莫司谷浓度/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䓬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。五酯胶囊较地尔硫䓬在CYP3A5表达型患者中对他克莫司血药浓度的提升作用更强。
关键词:    他克莫司      五酯胶囊      地尔硫䓬      血药浓度      CYP3A5基因多态性     
Effect of wuzhi capsules on the blood concentration of tacrolimus relative to diltiazem and CYP3A5 gene polymorphisms
CAI Yi-peng1,2, CHEN Quan-jin2, XIE Pei-hua2, SONG Hong-tao2
1. Department of Pharmacy, Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou 350009, China;
2. Department of Pharmacy, 900 Hospital of the Joint Logistics Team, Fuzhou 350025, China
Abstract:
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)3A5 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 CYP3A5*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 CYP3A5*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 CYP3A5*3 genotype in both the self-control and the control group. CYP3A5 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 CYP3A5 non-expressers. In CYP3A5 expressers wuzhi capsules had a greater ability relative to diltiazem to increase the blood concentration of tacrolimus.
Key words:    tacrolimus    Wuzhi capsule    diltiazem    blood concentration    CYP3A5 gene polymorphism   
收稿日期: 2019-08-09
DOI: 10.16438/j.0513-4870.2019-0636
基金项目: 福州总医院院立课题(2016L13).
通讯作者: 宋洪涛,Tel:86-591-22859459,E-mail:sohoto@vip.163.com
Email: sohoto@vip.163.com
相关功能
PDF(325KB) Free
打印本文
0
作者相关文章
蔡宜朋  在本刊中的所有文章
陈泉金  在本刊中的所有文章
谢培华  在本刊中的所有文章
宋洪涛  在本刊中的所有文章

参考文献:
[1] Cai YP, Chen QJ, Xie PH, et al. Advances in genetic polymorphisms that affect tacrolimus concentration[J]. China Pharm (中国药房), 2016, 27:3741-3744.
[2] Xin HW, Wu XC, Li Q, et al. Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers[J]. Br J Clin Pharmacol, 2007, 64:469-475.
[3] Xin HW, Li Q, Wu XC, et al. Effects of Schisandra sphenanthera extract on the blood concentration of tacrolimus in renal transplant recipients[J]. Eur J Clin Pharmacol, 2011, 67:1309-1311.
[4] Regazzi M, Iacona I, Alessiani M, et al. Interaction between FK506 and diltiazem in an animal model[J]. Transplant Proc, 1996, 28:1017-1018.
[5] Cai YP, Chen QJ, Xie PH, et al. Effect of wuzhi capsules on the blood concentration and safety of tarcrolimus compared with diltiazem[J]. Chin J Clin Pharmacol Ther (中国临床药理学与药物治疗学), 2019, 24:910-915.
[6] Cheng Y, Li H, Meng Y, et al. Effect of CYP3A5 polymorphism on the pharmacokinetics of tacrolimus and acute rejection in renal transplant recipients:experience at a single centre[J]. Int J Clin Pract Suppl, 2015, 4:16-22.
[7] Kagaya H, Niioka T, Saito M, et al. Prediction of tacrolimus exposure by CYP3A5 genotype and exposure of co-administered everolimus in Japanese renal transplant recipients[J]. Int J Mol Sci, 2018, 19:882.
[8] AlvarezElías AC, GarcíaRoca P, VelásquezJones L, et al. CYP3A5 genotype and time to reach tacrolimus therapeutic levels in renal transplant children[J]. Transplant Proc, 2016, 48:631-634.
[9] Pallet N, Etienne I, Buchler M, et al. Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype[J]. Am J Transplant, 2016, 16:2670-2675.
[10] Yousef AM, Qosa H, Bulatova N, et al. Effects of genetic polymorphism in CYP3A4 and CYP3A5 genes on tacrolimus dose among kidney transplant recipients[J]. Iran J Kidney Dis, 2016, 10:156.
[11] Yang Y, Xin HW, Liu F, et al. Study on the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 gene polymorphism[J]. China Pharm (中国药房), 2017, 28:581-585.
[12] Li JL, Wang XD, Chen SY, et al. Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients:from retrospective to prospective[J]. Pharmacogenomics J, 2011, 11:300-306.
[13] Hua YF, He J, Zhou HH, et al. CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population[J]. Clin Chim Acta, 2005, 353:187-192.
[14] Yu KS, Cho JY, Shin SG, et al. Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states[J]. Clin Pharmacol Ther, 2004, 76:104-112.