Drug dosing optimization in critically ill children under continuous renal replacement therapy: from basic concepts to the bedside model informed precision dosing

Optimizing drug dosage in critically ill children undergoing Continuous Renal Replacement Therapy (CRRT) is mandatory and challenging, given the many factors impacting pharmacokinetics and pharmacodynamics coupled with the vulnerability of this population. A good understanding of the mechanisms that determine drug elimination via the CRRT technique is useful to avoid prescription pitfalls, however limited by the high between and within subject variability. The developments of population pharmacokinetic and physiologically based pharmacokinetic models derived from in-vivo and in-vitro studies, are challenging, but remain the most appropriate tool to suggest adjusted dosage regimens for every patient, throughout treatment. We searched PubMed using the search string: ‘pediatrics OR children’ AN ‘continuous renal replacement therapy’ AND ‘pharmacokinetics’ AND ‘model informed precision dosing’ AND, ‘physiologically based pharmacokinetics,’ AND ‘therapeutic drug monitoring’ until January 2024, regardless of language or publication status. Familiarizing the pediatric intensivists with the therapeutic drug monitoring and providing clinicians the individualized prescribing software such as Model Informed Precision Dosing would be a significant step forward. The clinical benefit for patients remains to be demonstrated.

针对接受连续肾脏替代治疗（Continuous Renal Replacement Therapy, CRRT）的重症儿童优化药物剂量，既是临床必需之举，亦极具挑战——该人群生理脆弱，且药物代谢动力学（pharmacokinetics）与药效动力学（pharmacodynamics）受诸多因素共同影响。明晰经CRRT清除药物的机制有助于规避处方误区，但个体间与个体内的高变异性极大限制了相关认知的落地。基于体内（in-vivo）、体外（in-vitro）研究构建群体药代动力学（population pharmacokinetics）及基于生理的药代动力学模型（physiologically based pharmacokinetic models）虽颇具挑战，却仍是贯穿治疗全程、为每位患者推荐个体化给药调整方案的最优工具。本研究以“儿科（pediatrics） OR 儿童（children）” AND “连续肾脏替代治疗” AND “药代动力学（pharmacokinetics）” AND “模型指导精准给药（model informed precision dosing）” AND “基于生理的药代动力学” AND “治疗药物监测（therapeutic drug monitoring）”为检索式，在PubMed数据库中检索截至2024年1月的相关文献，未限制文献语言及发表状态。向儿科重症医师普及治疗药物监测相关知识，并为临床医师提供如模型指导精准给药（Model Informed Precision Dosing）这类个体化处方软件，将是该领域向前发展的重要一步。其对患者的临床获益仍有待进一步验证。