ArticleDrug metabolism and disposition: the biological fate of chemicals2013
Hepatobiliary disposition of 17-OHPC and taurocholate in fetal human hepatocytes: a comparison with adult human hepatocytes.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group.Clinical pharmacology and therapeutics · 2015Pooled it
- Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives.Pharmaceutics · 2023Review
- Effects of Pro-Inflammatory Cytokines on Hepatic Metabolism in Primary Human Hepatocytes.International journal of molecular sciences · 2022Article
- Clinical Significance and Potential Mechanisms of ATP Binding Cassette Subfamily C Genes in Hepatocellular Carcinoma.Frontiers in genetics · 2022Article
- Incorporating Ontogeny in Physiologically Based Pharmacokinetic Modeling to Improve Pediatric Drug Development: What We Know About Developmental Changes in Membrane Transporters.Journal of clinical pharmacology · 2019Review
- Hepatocyte transplantation: Consider infusion before incision.World journal of transplantation · 2017Review
- Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics.Clinical pharmacokinetics · 2016Review
- Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.Journal of pharmaceutical sciences · 2016Review
- Characterization of arsenic hepatobiliary transport using sandwich-cultured human hepatocytes.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Ontogeny of human hepatic and intestinal transporter gene expression during childhood: age matters.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Establishment of metabolism and transport pathways in the rodent and human fetal liver.International journal of molecular sciences · 2013Review
- Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Critical appraisal of the efficacy, safety, and patient acceptability of hydroxyprogesterone caproate injection to reduce the risk of preterm birth.Patient preference and adherence · 2013Article
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11 authors at 6 institutions in 3 countries.
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Abstract
Little information is available in the literature regarding the expression and activity of transporters in fetal human liver or cultured cells. A synthetic progesterone structural analog, 17α-hydroxyprogesterone caproate (17-OHPC), is used in the prevention of spontaneous abortion in women with a history of recurrent miscarriage (habitual abortion). 17-OHPC has been reported to traverse the placental barrier and gain access to fetal circulation. In this study, the role of transporters in the disposition of 17-OHPC in fetal and adult human hepatocytes was examined. Progesterone metabolites have been reported to induce trans-inhibition of bile acid transporter, ABCB11. Thus, we investigated the effect of 17-OHPC or its metabolites on [(3)H]taurocholic acid transport in sandwich-cultured human fetal and adult hepatocytes. 17-OHPC was taken up rapidly into the cells and transported out partially by an active efflux process that was significantly inhibited by cold temperature, cyclosporine, verapamil, and rifampin. The active efflux mechanism was observed in both adult and fetal hepatocyte cultures. 17-OHPC produced a concentration-dependent inhibition of taurocholate efflux into canaliculi in sandwich-cultured adult and fetal human hepatocytes. However, given the high concentrations required to cause inhibition of these transport processes, no adverse effects would be anticipated from therapeutic levels of 17-OHPC. We also evaluated the expression of various hepatic transporters (ABCB1, ABCB4, SLCO1B1, SLCO1B3, SLCO2B1, ABCB11, SLC10A1, ABCC2, ABCC3, ABCC4, and ABCG2) in fetal and adult hepatocytes. With the exception of ABCB4, all transporters examined were expressed, albeit at lower mRNA levels in fetal hepatocytes compared with adults.
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