| Title: | Cellular uptake properties of lamotrigine in human placental cell lines : Investigation of involvement of organic cation transporters (SLC22A1–5) |
| Authors: | Hasegawa, Nami Browse this author |
| Furugen, Ayako Browse this author →KAKEN DB |
| Ono, Kanako Browse this author |
| Koishikawa, Mai Browse this author |
| Miyazawa, Yuki Browse this author |
| Nishimura, Ayako Browse this author |
| Umazume, Takeshi Browse this author |
| Narumi, Katsuya Browse this author →KAKEN DB |
| Kobayashi, Masaki Browse this author →KAKEN DB |
| Iseki, Ken Browse this author →KAKEN DB |
| Keywords: | Antiepileptic drugs |
| BeWo |
| JEG-3 |
| Lamotrigine |
| OCTs |
| OCTNs |
| Placenta |
| Issue Date: | 29-Jan-2020 |
| Publisher: | Japanese Society for the Study of Xenobiotics（日本薬物動態学会）JSSX |
| Journal Title: | Drug Metabolism and Pharmacokinetics |
| Volume: | 35 |
| Issue: | 3 |
| Start Page: | 266 |
| End Page: | 273 |
| Publisher DOI: | 10.1016/j.dmpk.2020.01.005 |
| PMID: | 32303459 |
| Abstract: | Lamotrigine (LTG) is an important antiepileptic drug for the treatment of seizures in pregnant women with epilepsy. However, it is not known if the transport of LTG into placental cells occurs via a carrier-mediated pathway. The aim of this study was to investigate the uptake properties of LTG into placental cell lines (BeWo and JEG-3), and to determine the involvement of organic cation transporters (OCTs, SLC22A1-3) and organic cation/carnitine transporter (OCTNs, SLC22A4-5) in the uptake process. The uptake of LTG at 37 °C was higher than that at 4 °C. OCT1 and OCTNs were detected in both cell lines. The uptake of LTG was not greatly affected by the extracellular pH, Na-free conditions, or the presence of l-carnitine, suggesting that OCTNs were not involved. Although several potent inhibitors of OCTs (chloroquine, imipramine, quinidine, and verapamil) inhibited LTG uptake, other typical inhibitors had no effect. In addition, siRNA targeted to OCT1 had no significant effect on LTG uptake. The mRNA expression in human term placenta followed the order OCTN2 > OCT3 > OCTN1 > OCT1 ≈ OCT2. These observations suggested that LTG uptake into placental cells was carrier-mediated, but that OCTs and OCTNs were not responsible for the placental transport process. |
| Rights: | ©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/80312 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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