基于生理学的药代动力学模型
药代动力学
药物治疗
医学
药理学
重症监护医学
计算机科学
内科学
作者
Karel Allegaert,Mohammad Yaseen Abbasi,Pieter Annaert,Olusola Olafuyi
标识
DOI:10.1080/17425255.2022.2099836
摘要
There is a need for structured approaches to inform on pharmacotherapy in preterm neonates. With their proven track record up to regulatory acceptance, physiologically based pharmacokinetic (PBPK) modeling and simulation provide a structured approach, and hold the promise to support drug development in preterm neonates.Compared to general and pediatric use of PBPK modeling, its use to inform pharmacotherapy in preterms is limited. Using a systematic search (PBPK + preterm), we retained 25 records (20 research papers, 2 letters, 3 abstracts). We subsequently collated the published information on PBPK software packages (PK-Sim®, Simcyp®), and their applications and optimization efforts in preterm neonates. It is encouraging that applications cover a broad range of scenarios (pharmacokinetic-dynamic analyses, drug-drug interactions, developmental pharmacogenetics, lactation related exposure) and compounds (small molecules, proteins). Furthermore, specific compartments (cerebrospinal fluid, tissue) or (patho)physiologic processes (cardiac output, biliary excretion, first pass metabolism) are considered.Knowledge gaps exist, giving rise to various levels of uncertainty in PBPK applications in preterm neonates. To improve this, we need cross talk between clinicians and modelers to generate and integrate knowledge (PK datasets, system knowledge, maturational physiology and pathophysiology) to further refine PBPK models.
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