Zhou L-Y, Zuo X-C, Chen K, Wang J-L, Chen Q-J, Zhou Y-N, Yuan H, Ma Y, Zhu L-J, Peng Y-X, Ming Y-Z
Clinical Pharmacy and Pharmacology Research Institute, Third Xiangya Hospital, Central South University, Changsha, China.
Department of Transplantation, Third Xiangya Hospital, Central South University, Changsha, China.
J Clin Pharm Ther. 2016 Jun;41(3):341-7. doi: 10.1111/jcpt.12394. Epub 2016 May 5.
The calcium channel blocker diltiazem has been used widely as a cyclosporine (CsA)/tacrolimus-sparing agent. However, considerable interpatient variability in diltiazem's CsA/tacrolimus-sparing effect has been observed in many clinical studies. This study was carried out to investigate the impacts of the CYP3A41G and CYP3A53 genetic polymorphisms on the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients.
Two hundred and twenty-five Chinese renal transplant patients were genotyped for CYP3A41G and CYP3A53. The predose and post-dose plasma concentrations of diltiazem and its main metabolisms were determined by HPLC. The relationships between the genotypes and pharmacokinetics were investigated.
The dose-adjusted concentrations and pharmacokinetics of diltiazem and its main metabolites were significantly affected by CYP3A4 1G and CYP3A53 alleles. Patients with a CYP3A41/1 genotype were found to have a higher dose-adjusted trough concentration and AUC of diltiazem and its main metabolites compared with those with CYP3A41G1G(P<0·05). The dose-adjusted trough levels and AUC of diltiazem and its main metabolites were significantly lower in CYP3A511 carriers than in CYP3A5*3 carriers (P < 0·05).
The CYP3A41G and CYP3A53 genetic polymorphisms are closely related to the trough concentration/dose ratios and pharmacokinetics of diltiazem and its main metabolites in Chinese adult renal transplant patients.
钙通道阻滞剂地尔硫䓬已被广泛用作环孢素（CsA）/他克莫司的节约剂。然而，在许多临床研究中观察到地尔硫䓬的CsA/他克莫司节约效应存在相当大的患者间差异。本研究旨在探讨CYP3A41G和CYP3A53基因多态性对中国成年肾移植患者地尔硫䓬及其主要代谢产物的谷浓度/剂量比和药代动力学的影响。
对225例中国肾移植患者进行CYP3A41G和CYP3A53基因分型。采用高效液相色谱法测定地尔硫䓬及其主要代谢产物给药前和给药后的血浆浓度。研究基因型与药代动力学之间的关系。
CYP3A41G和CYP3A53等位基因对地尔硫䓬及其主要代谢产物的剂量调整浓度和药代动力学有显著影响。与CYP3A41G1G基因型患者相比，CYP3A41/1基因型患者的地尔硫䓬及其主要代谢产物的剂量调整谷浓度和AUC更高（P<0.05）。CYP3A511携带者的地尔硫䓬及其主要代谢产物的剂量调整谷水平和AUC显著低于CYP3A5*3携带者（P<0.05）。
CYP3A41G和CYP3A53基因多态性与中国成年肾移植患者地尔硫䓬及其主要代谢产物的谷浓度/剂量比和药代动力学密切相关。
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