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首页> 外文期刊>Pharmacological research: The official journal of The Italian Pharmacological Society >Feasibility of, and critical paths for mycophenolate mofetil Bayesian dose adjustment: pharmacological re-appraisal of a concentration-controlled versus fixed-dose trial in renal transplant recipients.
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Feasibility of, and critical paths for mycophenolate mofetil Bayesian dose adjustment: pharmacological re-appraisal of a concentration-controlled versus fixed-dose trial in renal transplant recipients.

机译：贝叶斯剂量调整霉酚酸酯的可行性和关键途径：肾移植受者中浓度对照与固定剂量试验的药理学重新评估。

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The aim of this study was to analyze retrospectively and critically the different steps of the individual dose adjustment procedure employed in the concentration-controlled (CC) versus fixed-dose trial Apomygre, which showed that mycophenolate mofetil (MMF) dose adjustment using a limited sampling strategy significantly reduced the risk of treatment failures and acute rejection in renal transplants at one year posttransplantation. The number of AUCs performed during the study and circumstances of collection, time of blood sampling, Bayesian mycophenolic acid (MPA) area-under-the-curve (AUC) estimation procedures and physicians' compliance with MMF dose recommendations were retrospectively analyzed. 92% of AUCs scheduled over the study were actually performed. Sampling times were very well respected. Bayesian estimation of MPA exposure was done by the pharmacologists locally in accordance with the protocol instructions and the AUC estimates obtained were virtually all confirmed a posteriori. On the other hand, a second AUC estimated by multiple linear regression could only be provided for 84% of the profiles and showed a large overestimation with respect to Bayesian estimates for AUC values between 10 and 55mgh/L. In the CC arm, a very good physicians' compliance was observed (85%) and application of the dose recommendations led to higher values of AUCs (42.1+/-14.6mgh/L versus 36.7+/-16.3mgh/L, p=0.0035) and to more AUCs in the target range (69% versus 56%, p=0.0343) than when dose recommendations were not applied. By analyzing in detail the feasibility criteria of MMF Bayesian dose adjustment, this study highlighted the requirements for successful extrapolation of the Apomygre trial results to routine practice: (i) respect of the PK sampling time-windows; (ii) use of relevant tools for accurate drug exposure estimation and dose adjustment calculation; and (iii) good compliance of the physicians with regard to the recommended doses.
机译：这项研究的目的是回顾性和批判性地分析浓度对照（CC）与固定剂量试验Apomygre中采用的个体剂量调整程序的不同步骤，该研究表明使用有限采样的麦考酚酸酯（MMF）剂量调整该策略显着降低了移植后一年的肾移植治疗失败和急性排斥反应的风险。回顾性分析了研究过程中进行的AUC数量，采集情况，采血时间，贝叶斯麦考酚酸（MPA）曲线下面积（AUC）估计程序以及医生对MMF剂量建议的依从性。该研究中安排的92％的AUC实际上已执行。采样时间非常受尊重。贝叶斯对MPA暴露的估计是由药理人员根据协议说明在当地进行的，所获得的AUC估计值实际上全部被证实是后验的。另一方面，通过多元线性回归估算的第二个AUC只能提供84％的剖面，并且相对于10至55mgh / L的AUC值，贝叶斯估算值显示出很大的高估。在CC组中，观察到很好的医师依从性（85％），采用剂量建议导致AUCs值更高（42.1 +/- 14.6mgh / L与36.7 +/- 16.3mgh / L，p =与未应用剂量建议时相比，目标范围内的AUC值更高（0.0035）（69％比56％，p = 0.0343）。通过详细分析MMF贝叶斯剂量调整的可行性标准，本研究强调了将Apomygre试验结果成功外推至常规实践的要求：（i）尊重PK采样时间窗口; （ii）使用相关工具进行准确的药物暴露估算和剂量调整计算; （iii）医师对推荐剂量的良好依从性。

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