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肾脏病与透析肾移植杂志 ›› 2012, Vol. 21 ›› Issue (4): 330-334.

• 论文 • 上一篇    下一篇

奥美拉唑对肾移植术后不同剂型麦考酚酸浓度的影响

  

  • 出版日期:2012-08-28 发布日期:2012-09-03

Effect of proton pump inhibitors on concentration of different preparations of mycophenolic acid in kidney transplantation recipients

  • Online:2012-08-28 Published:2012-09-03

摘要:

摘要  目的:观察质子泵抑制剂(PPI)奥美拉唑对两种不同剂型的麦考酚酸(MPA)药代动力学的影响。  方法:两组患者在肾移植术后分别给予不同剂型的MPA吗替麦考酚酯片(MMF)和麦考酚钠肠溶片(EC-MPS)抗排斥治疗,均联用环孢素和激素,并都在术后立即给予奥美拉唑预防治疗,持续至术后第7天停用,分别观察术后第3、7、10天MPA的血浆浓度、达峰时间、峰值,其中血浆MPA浓度采用HPLC法测定,分别采集服药前及后0.5、1、1.5、2、3、4、6、8、12小时全血标本,采用WinNonlin 5.2程序,按非房室模型进行药代动力学参数的计算每次MPA浓度的MPA- AUC0-12h值。比较奥美拉唑对MMF和EC-MPS的达峰时间、峰值浓度和MPA-AUC0-12h值的影响。  结果:MMF组在肾移植术后第3、7、10天达峰时间分别为1.50±0.71、 2.50±1.04、1.25±0.60(h),其中第7天较第3天达峰时间延后,第10天较第7天达峰时间明显提前(P<0.05),峰值浓度分别为7.69±2.25、8.95±5.60、9.87±3.82(ug/ml) (P>0.05),MPA-AUC0-12h分别为38.98±14.63、34.59±12.04、32.47±10.81 (mg.h.L-1)(P=0.325);EC-MPS组在肾移植术后第3、7、10天达峰时间分别为2.50±0.53、2.56±0.62、2.63±0.74(h)(P=0.939),峰值浓度分别为11.56±9.59、12.64±8.49、10.11±9.19(ug/ml)(P=0.687),MPA-AUC0-12h分别为 22.76±15.52、25.31±10.37、 16.68±14.77 (mg.h.L-1)(P=0.197)。MPA-AUC0-12h两组间比较第3、7、10天P值分别为0.065、0.382、0.05;达峰时间两组间比较第3、7、10天P值分别0.01、0.721、0.002;峰值浓度两组间比较P值分别为 0.878、0.328、0.505。  结论:奥美拉唑能明显延长MMF达峰时间,可能降低MMF的峰值浓度;但对 EC-MPS的药代动力学无影响。在肾移植术后应用MMF作为免疫抑制剂的患者术后应早期的检测MPA的浓度,及时调整MMF的剂量。

关键词: 肾移植 , 奥美拉唑 , 麦考酚酸  , 血药浓度

Abstract:

ABSTRACT  Objective:  To study the effect of proton pump inhibitors (PPI)  on pharmacokinetical changes of different preparations of mycophenolic acid in kidney transplantation recipients. Methodology: Sixteen renal transplant recipients were randomly divided into group Ⅰ(n=8, treated with mycophenolate mofetil) and group Ⅱ(n=8, treated with EC-MPS). All patients were treated with cyclosporin (sandimmun neoral) and adrenal cortex hormone, and PPI was administrated right after transplantation until the 7th day. The concentration of MPA, Tmax and Cmax were observed in the 3rd, 7th and 10th day. 1 ml blood was sampled before and 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h after drug administration. The plasma concentration of MPA was determined by HPLC-UV detection and the pharmacokinetic parameters were calculated by WinNonlin 5.2 using non-compartment model. Results: The main pharmacokinetic parameters were as follows: For group 1, Tmax was 1.50±0.71, 2.50±1.04, 1.25±0.60 (h) respectively on the 3rd, 7th and 10th day, Cmax was 7.69±2.25, 8.95±5.60, 9.87±3.82 (ug/ml) (P>0.05), and MPA-AUC0-12h was 38.9±14.6, 34.6±12.0, 32.5±10.8 (mg.h.L-1) (P=0.325). For group 2, Tmax was 2.50±0.53, 2.56±0.62, 2.63±0.74 (h) (P=0.939) on the 3rd, 7th and 10th day, Cmax was 11.6±9.59, 12.6±8.49, 10.1±9.19 (ug/ml) respectively (P=0.687), and MPA-AUC0-12h was 22.8±15.5, 25.3±10.4, 16.7±14.8 (mg.h.L-1) (P=0.197). P value of MPA-AUC0-12h between the two groups was 0.065, 0.382 and 0.05 on the 3rd, 7th and 10th day, tmax was 0.01, 0.721 and 0.002 respectively, and Cmax was 0.878, 0.328 and 0.505.  Conclusion: The Tmax of MMF was increased significantly with the use of PPI, and the Cmax of MMF showed some downward trend. However, PPI showed little effect on the pharmacokinetics of EC-MPS. MPA concentration should be detected early after transplantation in patients using MMF as immunosuppressant and the dose of MMF can be adjusted timely accordingly.

Key words:  kidney transplantation , proton pump inhibitors , mycophenolic acid