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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Dose Optimization in Kidney Disease: Opportunities for PBPK Modeling and Simulation
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Dose Optimization in Kidney Disease: Opportunities for PBPK Modeling and Simulation

机译：肾脏病剂量优化：PBPK建模与模拟的机会

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Kidney disease affects pharmacokinetic (PK) profiles of notonly renallycleared drugs butalso nonrenallycleared drugs.The impactof kidney disease on drug disposition has not been fully elucidated, but describing the extent of such impact is essential for conducting dose optimization in kidney disease. Accurate evaluation of kidney function has been a clinical interest for dose optimization, and more scientists pay attention and conduct research for clarifying the role of drug transporters, metabolic enzymes, and their interplay in drug disposition as kidney disease progresses. Physiologically based pharmacokinetic (PBPK) modeling and simulation can provide valuable insights for dose optimization in kidney disease. It is a powerful tool to integrate discrete knowledge from preclinical and clinical research and mechanistically investigate system- and drug-dependentfactors that maycontribute to the changes in PK profiles. PBPK-based prediction of drug exposures may be used a priori to adjust dosing regimens and thereby minimize the likelihood of drug-related toxicity.With real-time clinical studies, parameter estimation may be performed with PBPK approaches that can facilitate identification of sources of interindividual variability. PBPK modeling may also facilitate biomarker research that aids dose optimization in kidney disease. U.S. Food and Drug Administration guidances related to conduction of PK studies in kidney impairment and PBPK documentation provide the foundation for facilitating model-based dose-finding research in kidney disease.gggCKD, dose optimization, drug transporters, kidney function, metabolic enzymes, PBPK
机译：肾脏疾病不仅影响肾循环药物的药代动力学（PK），也影响非肾循环药物的药代动力学（PK）。肾脏疾病对药物处置的影响尚未完全阐明，但描述这种影响的程度对于肾脏疾病的剂量优化至关重要。准确评估肾功能一直是剂量优化的临床兴趣，随着肾脏疾病的进展，越来越多的科学家关注并开展研究，以阐明药物转运体、代谢酶及其在药物处置中的作用。基于生理学的药代动力学（PBPK）建模和模拟可以为肾脏疾病的剂量优化提供有价值的见解。它是一个强大的工具，可以整合来自临床前和临床研究的离散知识，并从机制上研究可能导致PK谱变化的系统和药物依赖因素。基于PBPK的药物暴露预测可用于预先调整给药方案，从而将药物相关毒性的可能性降至最低。通过实时临床研究，可以使用PBPK方法进行参数估计，这有助于识别个体间变异的来源。PBPK模型也可能有助于生物标记物研究，以帮助肾脏疾病的剂量优化。美国食品和药物管理局指南与PK研究在肾脏损害和PBPK文献中的传导有关，为促进基于模型的肾脏疾病的剂量发现研究提供了基础。gggCKD、剂量优化、药物转运体、肾功能、代谢酶、PBPK

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