Department of Pharmacology, School of Medicine, University of Patras, Rion, Greece.
Indian J Pharmacol. 2011 Jul;43(4):385-8. doi: 10.4103/0253-7613.83106.
Atherosclerosis is a significant factor affecting long-term outcome in renal transplant recipients. Studies have been conducted to determine the pharmacogenomic pathways involved in statin efficacy, efficiency, and adverse effect likelihood. However, little is known about the influence of statins on tacrolimus kinetics. The aim of this study was to investigate possible pharmacological interactions between tacrolimus and statins in CYP3A5 non-expressors, renal transplant recipients.
Twenty-four patients, treated with tacrolimus (n=24), methylprednisolone (n=24), and mycophenolate mofetil (n=19)/azathioprine (n=1)/everolimus (n=4), participated in the study. After an observation time of 112±36 days, statins, namely, atorvastatin (n=12), simvastatin (n=8), pravastatin (n=2), or fluvastatin (n=2), were administered for additional 101±34 days. DNA was extracted from whole blood sample and polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for CYP3A5 genotyping. Student's t-test and Mann-Whitney test were used to test the significance of difference in variables that passed or did not pass Kolmogorov's normality test, respectively.
No statistically significant difference was observed in tacrolimus daily dose, concentration, concentration/dose ratio, and volume of distribution before and during the administration of statins. Statistically significant decrease in serum cholesterol was observed after initiation of statins. Renal and hepatic function remained unchanged and no skeletal muscle abnormalities were reported.
The results of this study show that tacrolimus and statins do not interact in terms of efficacy, efficiency, and adverse effect likelihood. No significant clinical interaction or effect was observed, even with the use of atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus.
动脉粥样硬化是影响肾移植受者长期预后的重要因素。已经进行了研究以确定涉及他汀类药物疗效、效率和不良反应可能性的药物基因组学途径。然而，对于他汀类药物对他克莫司动力学的影响知之甚少。本研究旨在研究 CYP3A5 非表达者肾移植受者中他克莫司和他汀类药物之间可能存在的药理相互作用。
24 例接受他克莫司（n=24）、甲基强的松龙（n=24）和霉酚酸酯（n=19）/硫唑嘌呤（n=1）/依维莫司（n=4）治疗的患者参加了这项研究。在观察时间 112±36 天后，再给予阿托伐他汀（n=12）、辛伐他汀（n=8）、普伐他汀（n=2）或氟伐他汀（n=2）等他汀类药物 101±34 天。从全血样本中提取 DNA，然后进行聚合酶链反应，接着进行限制性片段长度多态性分析以进行 CYP3A5 基因分型。对于通过和未通过柯尔莫哥洛夫正态性检验的变量，分别使用学生 t 检验和曼-惠特尼检验来检验差异的显著性。
在给予他汀类药物之前和期间，他克莫司的日剂量、浓度、浓度/剂量比和分布容积没有观察到统计学上的显著差异。开始使用他汀类药物后，血清胆固醇显著下降。肾功能和肝功能保持不变，未报告骨骼肌异常。
本研究结果表明，他克莫司和他汀类药物在疗效、效率和不良反应可能性方面没有相互作用。即使使用阿托伐他汀或辛伐他汀等代谢物为 CYP3A4 的他汀类药物，也未观察到明显的临床相互作用或影响。
