Premium
Evaluation of Maternal Drug Exposure Following the Administration of Antenatal Corticosteroids During Late Pregnancy Using Physiologically‐Based Pharmacokinetic Modeling
Author(s) -
Ke Alice Ban,
Milad Mark A.
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1438
Subject(s) - pharmacokinetics , pregnancy , medicine , drug , pharmacology , drugs in pregnancy , drug administration , obstetrics , fetus , intensive care medicine , biology , genetics
Betamethasone and dexamethasone are the most widely studied antenatal corticosteroids ( ACS ) administered to pregnant women, just prior to the birth of a preterm neonate, to accelerate fetal lung maturation. Although betamethasone, predominantly used in developed countries, has been shown to be an effective and safe intervention for reducing neonatal mortality, the choice of ACS and optimal dosing in low and middle income countries ( LMIC s) remains unclear. This is primarily because the exposure–response relationships have not been established for ACS despite the long history of use. As the first step toward the optimal use of ACS in LMIC s, we developed physiologically‐based pharmacokinetic (PBPK) models to describe the kinetics of ACS following i.v., p.o., or i.m. dosing. In vitro data describing the cytochrome P450 3A4 enzyme contribution were incorporated and this was refined using clinical data. The models can be applied prospectively to predict kinetics of ACS in pregnant women receiving various dosing regimens.