Predicting fetal exposure of crizotinib during pregnancy: Combining human ex vivo placenta perfusion data with physiologically-based pharmacokinetic modeling

Roelofsen, D; Hove, Hedwig van; Bukkems, Vera E.; Rüssel, Frans G. M.; Eliesen, Gaby A M; Greupink, Rick

doi:10.1016/j.tiv.2022.105471

Cited by 4 publications

(1 citation statement)

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“…Placenta-on-a-chip and other experimental in vitro approaches ( Myllynen and Vahakangas, 2013 ) have the potential to provide important information; however, these techniques currently lack integration of changes that occur throughout pregnancy. Excellent examples of combining multiple approaches to estimate human fetal drug exposure have recently been published ( Balhara et al, 2022 ; Roelofsen et al, 2022 ). Alternative approaches can provide insight into fetal drug exposure during human pregnancy and inform dosing in clinical trials that include pregnant individuals.…”

Section: Discussionmentioning

confidence: 99%

Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure

et al. 2023

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Prescription drug use is prevalent during pregnancy, yet there is limited knowledge about maternal-fetal safety and efficacy of this drug use because pregnant individuals have historically been excluded from clinical trials. Underrepresentation has resulted in a lack of data available to estimate or predict fetal drug exposure. Approaches to study fetal drug pharmacology are limited and must be evaluated for feasibility and accuracy. Anatomic and physiological changes throughout pregnancy fluctuate based on gestational age and can affect drug pharmacokinetics (PK) for both mother and fetus. Drug concentrations have been studied throughout different stages of gestation and at or following delivery in tissue and fluid biospecimens. Sampling amniotic fluid, umbilical cord blood, placental tissue, meconium, umbilical cord tissue, and neonatal hair present surrogate options to quantify and characterize fetal drug exposure. These sampling methods can be applied to all therapeutics including small molecule drugs, large molecule drugs, conjugated nanoparticles, and chemical exposures. Alternative approaches to determine PK have been explored, including physiologically based PK modeling, in vitro methods, and traditional animal models. These alternative approaches along with convenience sampling of tissue or fluid biospecimens can address challenges in studying maternal-fetal pharmacology. In this narrative review, we 1) present an overview of the current understanding of maternal-fetal drug exposure; 2) discuss biospecimen-guided sampling design and methods for measuring fetal drug concentrations throughout gestation; and 3) propose methods for advancing pharmacology research in the maternal-fetal population.

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Section: Discussionmentioning

confidence: 99%