title: Effects of Antiviral Drugs on Organic Anion Transport in Human Placental BeWo Cells.
abstract: Placental drug transfer is important for achieving better pharmacotherapy in pregnant women and in fetuses. In the present study, we examined the effects of anti-hepatitis C virus (HCV) and anti-HIV drugs on organic anion transport in human placental BeWo cells. The cellular uptake of two fluorescence organic anions, 8-(2-[fluoresceinyl]aminoethylthio)adenosine-3',5'-cyclic monophosphate (8-FcAMP) and fluorescein, was temperature and concentration dependent. The Michaelis constant (Km) and the maximum uptake rate (Vmax) for 8-FcAMP transport in BeWo cells were estimated to be 6.45 ± 0.75 μM and 25.55 ± 5.93 pmol/mg protein/10 min, respectively. The Km and Vmax values for fluorescein uptake were estimated to be 31.2 ± 11.8 μM and 510.9 ± 90.6 pmol/mg protein/10 min, respectively. Several known substrates of organic anion transporters in human placenta, including atorvastatin, glibenclamide, estrone-3-sulfate, and rifampin, inhibited cellular uptake of 8-FcAMP and fluorescein in BeWo cells. Transport of 8-FcAMP and fluorescein was inhibited by the antiviral drugs boceprevir, telaprevir, elvitegravir, and maraviroc. These findings suggest that some antiviral drugs are sufficiently potent to influence placental drug transfer and cause drug-drug interactions.
authors.affiliation: School of Pharmacy, Aichi Gakuin University, Nagoya, Japan nabekura@dpc.agu.ac.jp.
authors.forename: Tomohiro
authors.identifier: http://orcid.org/0000-0002-7139-2270
authors.initials: T
authors.lastname: Nabekura
authors.affiliation: School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kamiya
authors.affiliation: School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uwai
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001692:Biological Transport; D002460:Cell Line; D004347:Drug Interactions; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D027361:Organic Anion Transporters / Q000187:drug effects* / Q000378:metabolism*; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D000998:Antiviral Agents; D005456:Fluorescent Dyes; D027361:Organic Anion Transporters