Departments of Pharmacology.
Ther Clin Risk Manag. 2010 Jun 24;6:265-9. doi: 10.2147/tcrm.s11501.
As proton pump inhibitors share CYP3A4 enzyme with tacrolimus for their hepatic elimination, they potentially affect its pharmacokinetics, most prominently in patients with CYP2C19 or CYP3A5 gene mutations. Our aim was to investigate the impact of omeprazole on tacrolimus pharmacokinetics in CYP3A5 non-expressors, kidney transplant recipients.
Twelve patients (five males/seven females) were observed for 175 +/- 92.05 days. Omeprazole (20 mg pos) was administrated for 75.83 +/- 45.17 days. Immunosuppressant regimen consisted of tacrolimus (n = 12), methylprednisolone (n = 10), mycophenolate mofetil (n = 11), azathioprine (n = 1), and everolimus (n = 2). Patient's body weight, coadministered drugs, and tacrolimus trough levels were monitored. Aspartate and alanine aminotransferase, gamma-glutamyltransferase, and bilirubin were used for evaluating hepatic function. Tacrolimus kinetics were estimated with daily dose, concentration, dose adjusted concentration, and volume of distribution with and without coadministration of omeprazole. CYP3A5 genotyping was performed with PCR followed by restriction fragment length polymorphism analysis. Statistical analysis was performed with Prism 4 software (GraphPad Software, Inc).
No statistically significant difference was observed in tacrolimus kinetics and hepatic function during coadministration of omeprazole.
Our results let us propose that there is no need for more frequent therapeutic drug monitoring of tacrolimus when coadministrated with omeprazole in CYP3A5 nonexpressors, though prospective studies with more patients and longer observation period are needed to confirm these findings.
质子泵抑制剂（PPI）与他克莫司通过细胞色素 P4503A4（CYP3A4）代谢，因此它们可能影响他克莫司的药代动力学，在 CYP2C19 或 CYP3A5 基因突变的患者中更为明显。我们的目的是研究 CYP3A5 无表达者肾移植患者中奥美拉唑对他克莫司药代动力学的影响。
观察 12 例患者（5 例男性/7 例女性）175±92.05 天。奥美拉唑（20mg，po）给药 75.83±45.17 天。免疫抑制剂方案包括他克莫司（n=12）、甲泼尼龙（n=10）、霉酚酸酯（n=11）、硫唑嘌呤（n=1）和依维莫司（n=2）。监测患者体重、合并用药和他克莫司谷浓度。天冬氨酸转氨酶、丙氨酸转氨酶、γ-谷氨酰转移酶和胆红素用于评估肝功能。评估有无奥美拉唑合并用药时，他克莫司的动力学参数包括每日剂量、浓度、剂量调整浓度和分布容积。采用聚合酶链反应（PCR）联合限制性片段长度多态性分析进行 CYP3A5 基因分型。采用 Prism 4 软件（GraphPad Software，Inc.）进行统计分析。
奥美拉唑合并用药期间，他克莫司的动力学和肝功能无统计学差异。
我们的结果表明，CYP3A5 无表达者肾移植患者中，合并使用奥美拉唑时无需更频繁地监测他克莫司的血药浓度，但需要更多患者和更长观察期的前瞻性研究来证实这些发现。
