Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling.

Autor: van Hoogdalem MW; Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.; James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45229, USA., Tanaka R; Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA., Abduljalil K; Certara UK Limited, Simcyp Division, Sheffield S1 2BJ, UK., Johnson TN; Certara UK Limited, Simcyp Division, Sheffield S1 2BJ, UK., Wexelblatt SL; Division of Neonatology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.; Center for Addiction Research, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA., Akinbi HT; Division of Neonatology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA., Vinks AA; Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.; Center for Addiction Research, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA., Mizuno T; Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.; Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.; Center for Addiction Research, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2024 Mar 08; Vol. 16 (3). Date of Electronic Publication: 2024 Mar 08.
DOI: 10.3390/pharmaceutics16030375
Abstrakt: Buprenorphine readily crosses the placenta, and with greater prenatal exposure, neonatal opioid withdrawal syndrome (NOWS) likely grows more severe. Current dosing strategies can be further improved by tailoring doses to expected NOWS severity. To allow the conceptualization of fetal buprenorphine exposure, a maternal-fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0). Buprenorphine transplacental passage was predicted from its physicochemical properties. The maternal-fetal PBPK model integrated reduced transmucosal absorption driven by lower salivary pH and induced metabolism observed during pregnancy. Maternal pharmacokinetics was adequately predicted in the second trimester, third trimester, and postpartum period, with the simulated area under the curve from 0 to 12 h, apparent clearance, and peak concentration falling within the 1.25-fold prediction error range. Following post hoc adjustment of the likely degree of individual maternal sublingual absorption, umbilical cord blood concentrations at delivery (n = 21) were adequately predicted, with a geometric mean ratio between predicted and observed fetal concentrations of 1.15 and with 95.2% falling within the 2-fold prediction error range. The maternal-fetal PBPK model developed in this study can be used to forecast fetal buprenorphine exposure and would be valuable to investigate its correlation to NOWS severity.
Databáze: MEDLINE
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