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Pharm Res. 2004 Dec;21(12):2279-92.

Area/moment and compartmental modeling of pharmacokinetics during pregnancy: applications to maternal/fetal exposures to corticosteroids in sheep and rats.

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Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.



The 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.


Betamethasone 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.


Polyexponential 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.


Generalized 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.

[Indexed for MEDLINE]

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