Pediatric Drug-Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations.
Pediatric Drug-Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations.
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DOI：
10.1002/jcph.1881
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发表时间：
2021-06
影响因子：
2.9
通讯作者：
Sinha J
中科院分区：
文献类型：
--
作者：
Gonzalez D;Sinha J
住院儿科患者和门诊治疗的复杂或慢性疾病患者通常会处方多种药物，导致药物相互作用（DDI）的风险增加。尽管在药物开发期间常规在健康成人志愿者中进行专门的DDI评价，但由于伦理、后勤和方法学方面的挑战，很少在儿科患者中进行。在缺乏儿科DDI评价的情况下，成人DDI数据通常外推至儿科患者。然而，由于年龄依赖性生理变化可能影响药物处置或反应，以及由于与药物相关的其他因素（例如，剂量，制剂）和患者群体（例如，疾病状态、肥胖）。因此，DDI幅度需要在儿童中与成人分开评估，尽管缺乏儿科人群的临床DDI数据使得该评价具有挑战性。因此，儿科DDI评估依赖于所用药物计量学方法的预测性能，例如基于群体和生理学的药代动力学建模。因此，需要仔细考虑，以充分考虑这些模型中的年龄依赖性生理变化，从而为此类未经测试的DDI场景建立高置信水平。这篇综述文章总结了与药物、患者人群和方法学相关的关键考虑因素，以及它们如何影响儿科人群的DDI评价。
Hospitalized pediatric patients and those with complex or chronic conditions treated on an outpatient basis are commonly prescribed multiple drugs resulting in an increased risk for drug-drug interactions (DDIs). Although dedicated DDI evaluations are routinely performed in healthy adult volunteers during drug development, they are rarely performed in pediatric patients due to ethical, logistical, and methodological challenges. In the absence of pediatric DDI evaluations, adult DDI data are often extrapolated to pediatric patients. However, the magnitude of a DDI in pediatric patients may differ from adults because of age-dependent physiological changes that can impact drug disposition or response, and due to other factors related to the drug (e.g., dose, formulation) and the patient population (e.g., disease states, obesity). Therefore, the DDI magnitude needs to be assessed in children separately from adults, although a lack of clinical DDI data in pediatric populations makes this evaluation challenging. As a result, pediatric DDI assessment relies on the predictive performance of the pharmacometric approaches used, such as population and physiologically-based pharmacokinetic modeling. Therefore, careful consideration needs to be given to adequately account for the age-dependent physiological changes in these models to build a high confidence level for such untested DDI scenarios. This review article summarizes the key considerations related to the drug, patient population, and methodology, and how they can impact DDI evaluation in the pediatric population.
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