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首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >Constructing a prediction interval for time to reach a threshold concentration based on a population pharmacokinetic analysis: an application to basiliximab in renal transplantation.
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Constructing a prediction interval for time to reach a threshold concentration based on a population pharmacokinetic analysis: an application to basiliximab in renal transplantation.

机译：基于群体药代动力学分析，构建达到阈值浓度的时间的预测间隔：在巴利昔单抗在肾移植中的应用。

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摘要

Basiliximab is an immunosuppressant chimeric monoclonal antibody directed to the human interleukin-2 receptor alpha-chain used for prevention of acute rejection episodes in organ transplantation. The minimally effective serum concentration necessary to saturate receptor epitopes in kidney transplant patients is 0.2 microgram/ml. To guide dose selection for Phase 3 efficacy trials, a population pharmacostatistical model was fitted to intensively sampled Phase 2 pharmacokinetic data. This served as a basis from which to examine candidate dose regimens with respect to the duration over which receptor-saturating concentrations would be achieved posttransplant. Three prediction methods were assessed: one based on simulations, and two others based on first-order approximation using either inverse regression or inversion of confidence intervals. An 80% prediction interval was generated by each method to evaluate its predictive performance against prospectively collected Phase 3 data in 39 renal transplant patients who received two injections of 20 mg basiliximab, one prior to surgery and one on Day 4 posttransplant. All methods provided correct prediction of the duration of receptor-saturating concentration. As anticipated, the best performance was obtained from the simulation method which predicted 30 values in the 80% prediction interval, 19.7-52.7 days. The actually observed 80% interval from the Phase 3 data was 23.7-58.3 days.
机译：Basiliximab是针对人白介素2受体α链的免疫抑制剂嵌合单克隆抗体，用于预防器官移植中的急性排斥反应。使肾移植患者的受体表位饱和所需的最低有效血清浓度为0.2微克/毫升。为了指导3期功效试验的剂量选择，将人群药代统计模型拟合为密集采样的2期药代动力学数据。这是检查移植后达到受体饱和浓度持续时间的候选剂量方案的基础。评估了三种预测方法：一种基于模拟，另外两种基于一阶近似，使用逆回归或置信区间反演。每种方法均产生80％的预测间隔，以评估39位接受两次20 mg巴利昔单抗注射的肾移植患者的前瞻性收集的3期数据的预测性能，一次是在手术前，另一次是在移植后第4天。所有方法都可以正确预测受体饱和浓度的持续时间。正如预期的那样，从模拟方法获得了最佳性能，该方法在80％的预测间隔（19.7-52.7天）中预测了30个值。从阶段3数据实际观察到的80％间隔为23.7-58.3天。

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