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Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5).
Drug Metab Pharmacokinet. 2020 Jun; 35(3):266-273.DM

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.

Authors+Show Affiliations

Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.Department of Pharmacy, Hokkaido University Hospital, Sapporo, Japan.Department of Obstetrics, Hokkaido University Hospital, Sapporo, Japan.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan. Electronic address: masaki@pharm.hokudai.ac.jp.Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan. Electronic address: ken-i@pharm.hokudai.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32303459

Citation

Hasegawa, Nami, et al. "Cellular Uptake Properties of Lamotrigine in Human Placental Cell Lines: Investigation of Involvement of Organic Cation Transporters (SLC22A1-5)." Drug Metabolism and Pharmacokinetics, vol. 35, no. 3, 2020, pp. 266-273.
Hasegawa N, Furugen A, Ono K, et al. Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5). Drug Metab Pharmacokinet. 2020;35(3):266-273.
Hasegawa, N., Furugen, A., Ono, K., Koishikawa, M., Miyazawa, Y., Nishimura, A., Umazume, T., Narumi, K., Kobayashi, M., & Iseki, K. (2020). Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5). Drug Metabolism and Pharmacokinetics, 35(3), 266-273. https://doi.org/10.1016/j.dmpk.2020.01.005
Hasegawa N, et al. Cellular Uptake Properties of Lamotrigine in Human Placental Cell Lines: Investigation of Involvement of Organic Cation Transporters (SLC22A1-5). Drug Metab Pharmacokinet. 2020;35(3):266-273. PubMed PMID: 32303459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular uptake properties of lamotrigine in human placental cell lines: Investigation of involvement of organic cation transporters (SLC22A1-5). AU - Hasegawa,Nami, AU - Furugen,Ayako, AU - Ono,Kanako, AU - Koishikawa,Mai, AU - Miyazawa,Yuki, AU - Nishimura,Ayako, AU - Umazume,Takeshi, AU - Narumi,Katsuya, AU - Kobayashi,Masaki, AU - Iseki,Ken, Y1 - 2020/01/29/ PY - 2019/10/02/received PY - 2020/01/07/revised PY - 2020/01/26/accepted PY - 2020/4/19/pubmed PY - 2020/4/19/medline PY - 2020/4/19/entrez KW - Antiepileptic drugs KW - BeWo KW - JEG-3 KW - Lamotrigine KW - OCTNs KW - OCTs KW - Placenta SP - 266 EP - 273 JF - Drug metabolism and pharmacokinetics JO - Drug Metab. Pharmacokinet. VL - 35 IS - 3 N2 - 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. SN - 1880-0920 UR - https://www.unboundmedicine.com/medline/citation/32303459/Cellular_uptake_properties_of_lamotrigine_in_human_placental_cell_lines:_Investigation_of_involvement_of_organic_cation_transporters_(SLC22A1-5) L2 - https://linkinghub.elsevier.com/retrieve/pii/S1347-4367(20)30010-0 DB - PRIME DP - Unbound Medicine ER -
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