Current and future physiologically based pharmacokinetic (PBPK) modeling approaches to optimize pharmacotherapy in preterm neonates.

Autor:	Allegaert K; Department of Pharmaceutical and Pharmacological Sciences.; Department of Development and Regeneration and Regeneration, KU Leuven, Leuven, Belgium.; Leuven Child and Youth Institute, KU Leuven, Leuven, Belgium.; Department of Clinical Pharmacy, Erasmus MC,Rotterdam, the Netherlands., Abbasi MY; Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA., Annaert P; Department of Pharmaceutical and Pharmacological Sciences., Olafuyi O; School of Life Sciences, University of Nottingham, Nottingham, UK.
Jazyk:	angličtina
Zdroj:	Expert opinion on drug metabolism & toxicology [Expert Opin Drug Metab Toxicol] 2022 May; Vol. 18 (5), pp. 301-312. Date of Electronic Publication: 2022 Jul 15.
DOI:	10.1080/17425255.2022.2099836
Abstrakt:	Introduction: 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. Areas Covered: 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. Expert Opinion: 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.
Databáze:	MEDLINE
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