ArticlePharmaceutical research2004
Area/moment and compartmental modeling of pharmacokinetics during pregnancy: applications to maternal/fetal exposures to corticosteroids in sheep and rats.
Article in Pharmaceutical research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Systematic Quantitative Analysis of Fetal Dexamethasone Exposure and Fetal Lung Maturation in Pregnant Animals: Model Informed Dexamethasone Precision Dose Study.ACS pharmacology & translational science · 2024Article
- Antenatal corticosteroids: a reappraisal of the drug formulation and dose.Pediatric research · 2021Review
- Transitioning from Basic toward Systems Pharmacodynamic Models: Lessons from Corticosteroids.Pharmacological reviews · 2020Review
- Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat.The Journal of endocrinology · 2017Article
- Ontogeny and the effects of exogenous and endogenous glucocorticoids on tight junction protein expression in ovine cerebral cortices.Brain research · 2009Article
- Betamethasone for lung maturation: testing dose and formulation in fetal sheep.American journal of obstetrics and gynecology · 2007Article
- Quantification of dexamethasone and corticosterone in rat biofluids and fetal tissue using highly sensitive analytical methods: assay validation and application to a pharmacokinetic study.Biomedical chromatography : BMC · 2007Article
- Stability of dexamethasone sodium phosphate in rat plasma.International journal of pharmaceutics · 2005Article
- Betamethasone pharmacokinetics after two prodrug formulations in sheep: implications for antenatal corticosteroid use.Drug metabolism and disposition: the biological fate of chemicals · 2005Article
- Comparison of dexamethasone pharmacokinetics in female rats after intravenous and intramuscular administration.Biopharmaceutics & drug disposition · 2005Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
purposeThe pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed.
methodsBetamethasone in the maternal/fetal circulations of sheep was measured by HPLC after maternal intramuscular injection (n = 4) of 170 microg kg(-1) of a depot formulation. Additional data for beta-methasone in sheep and dexamethasone pharmacokinetics in rats were obtained from the literature. Area/Moment equations were derived using mass balance concepts, statistical moments, and Laplace theory. Area/Moment analysis, compartmental modeling, and allometric scaling to man for betamethasone were performed using WinNonlin and ADAPT II programs.
resultsPolyexponential maternal/fetal profiles for corticosteroids were observed. Clearance terms for corticosteroid transfer from fetus to mother were 4-fold higher than the clearance term for transfer in the opposite direction. A placental efflux process may restrict fetal access of corticosteroids which are known PGP substrates. The elimination clearance estimates indicate that fetal metabolism plays a minor role in corticosteroid elimination.
conclusionsGeneralized and specific models for maternal/fetal pharmacokinetics were developed. An efflux transport mechanism, such as the known placental expression of PGP, could explain the limited fetal exposure of corticosteroids.
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Registered trials
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