Transplacental pharmacokinetics of glyburide, rhodamine 123, and BODIPY FL prazosin: effect of drug efflux transporters and lipid solubility
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19779128
DOI
10.1124/jpet.109.160564
PII: jpet.109.160564
Knihovny.cz E-zdroje
- MeSH
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry metabolismus MeSH
- biologický transport MeSH
- glibenklamid chemie farmakokinetika MeSH
- krysa rodu Rattus MeSH
- lipidy chemie MeSH
- maternofetální výměna látek MeSH
- P-glykoprotein metabolismus MeSH
- perfuze MeSH
- placenta metabolismus MeSH
- prazosin analogy a deriváty chemie farmakokinetika MeSH
- rhodamin 123 chemie farmakokinetika MeSH
- rozpustnost MeSH
- sloučeniny boru chemie farmakokinetika MeSH
- substrátová specifita MeSH
- techniky in vitro MeSH
- těhotenství MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry MeSH
- Abcg2 protein, rat MeSH Prohlížeč
- BODIPY-FL prazosin MeSH Prohlížeč
- glibenklamid MeSH
- lipidy MeSH
- P-glykoprotein MeSH
- prazosin MeSH
- rhodamin 123 MeSH
- sloučeniny boru MeSH
Breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp) are the most abundantly expressed ATP-binding cassette (ABC) drug transporters in the placenta. They recognize a large, partly overlapping spectrum of chemically unrelated compounds and affect their transplacental passage. In this study we investigate the effect of Bcrp and P-gp on the transplacental pharmacokinetics of their specific and common substrates employing the technique of dually perfused rat placenta. We show that the clearance of rhodamine 123 (P-gp substrate), glyburide (BCRP substrate) and BODIPY FL prazosin (P-gp and BCRP substrate) in fetal-to-maternal direction is 11, 11.2 and 4 times higher, respectively, than that in the maternal-to-fetal direction. In addition, all of these substances were found to be transported from the fetal compartment even against concentration gradient. We thus demonstrate the ability of placental ABC transporters to hinder maternal-to-fetal and accelerate fetal-to-maternal transport in a concentration-dependent manner. However, by means of pharmacokinetic modeling we describe the inverse correlation between lipid solubility of a molecule and its active transport by placental ABC efflux transporters. Therefore, in the case of highly lipophilic substrates, such as BODIPY FL prazosin in this study, the efficacy of efflux transporters to pump the molecule back to the maternal circulation is markedly limited.
Citace poskytuje Crossref.org
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