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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Distribution of saquinavir, methadone, and buprenorphine in maternal brain, placenta, and fetus during two different gestational stages of pregnancy in mice
Journal of Pharmaceutical Sciences, Volume 98, No. 8, Year 2009
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Description
Efflux transporters such as P-glycoprotein (P-gp) play a critical role in the maternal-to-fetal and blood-to-brain transfer of many drugs. Using a mouse model, the effects of gestational age on P-gp and MRP expression in the placenta and brain were evaluated. P-gp protein levels in the placenta and brain were greater at mid-gestation (gd 13) than late-gestation (gd 18). Likewise, brain MRP1 levels were greater at mid-gestation, whereas, placental levels were greater at late-gestation. To evaluate these effects on drug disposition, concentrations of [3H]saquinavir, [3H]methadone, [ 3H]buprenorphine, and the paracellular marker, [14C] mannitol were measured in plasma, brain, placenta, and fetal samples after i.v. administrations to nonpregnant and pregnant mice. Following i.v. administration, [3H]saquinavir placenta-to-plasma and fetal-to-plasma ratios were significantly greater in lategestation mice versus mid-gestation. Furthermore, late-gestation mice experienced significant increases in the [ 3H]saquinavir and [3H]methadone brain-to-plasma ratios 60 min after dosing relative to mid-gestation (p<0.05). No significant differences were observed in these tissue-to-plasma ratios for buprenorphine or mannitol. Repeated dosing (three doses, once daily) decreased the differential uptake of [3H]saquinavir in brain but potentiated it in the fetus. These results suggest that differential expression of P-gp and possibly MRP1 contributes to the gestational-induced changes in brain and fetal uptake of saquinavir. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association.
Authors & Co-Authors
Coles, Lisa D.
United States, Baltimore
University of Maryland School of Pharmacy
Lee, Insong James
United States, Baltimore
Notre Dame of Maryland University
Hassan, Hazem Emad Eldin
Egypt, Helwan
Faculty of Pharmacy
Eddington, Natalie D.
United States, Baltimore
University of Maryland School of Pharmacy
Statistics
Citations: 35
Authors: 4
Affiliations: 3
Identifiers
Doi:
10.1002/jps.21644
ISSN:
00223549
e-ISSN:
15206017
Research Areas
Maternal And Child Health
Sexual And Reproductive Health