Faropenem transport across the renal epithelial luminal membrane via inorganic phosphate transporter Npt1

Hiroshi Uchino, Ikumi Tamai, Hikaru Yabuuchi, Kayoko China, Ken Ichi Miyamoto, Eiji Takeda, Akira Tsuji

研究成果: Article査読

27 被引用数 (Scopus)

抄録

We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression system. Faropenem (an oral penem antibiotic) was transported via Npt1 with a Michaelis-Menten constant of 0.77 ± 0.34 mM in a sodium-independent but chloride ion-sensitive manner. When the concentration of chloride ions was increased, the transport activity of faropenem by Npt1 was decreased. Since the concentration gradient of chloride ions is in the lumen-to-intracellular direction, faropenem is expected to be transported from inside proximal tubular cells to the lumen. So, we tested the release of faropenem from Xenopus oocytes. The rate of efflux of faropenem from Npt1- expressing oocytes was about 9.5 times faster than that from control water- injected Xenopus oocytes. Faropenem transport by Npt1 was significantly inhibited by β-lactam antibiotics such as benzylpenicillin, ampicillin, cephalexin, and cefazolin to 24.9, 40.5, 54.4, and 26.2% of that for the control, respectively. Zwitterionic β-lactam antibiotics showed lesser inhibitory effects on faropenem uptake than anionic derivatives, indicating that Npt1 preferentially transports anionic compounds. Other anionic compounds, such as indomethacin and furosemide, and the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid significantly inhibited faropenem uptake mediated by Npt1. In conclusion, our results suggest that Npt1 participates in the renal secretion of penem antibiotics.

本文言語English
ページ(範囲)574-577
ページ数4
ジャーナルAntimicrobial agents and chemotherapy
44
3
DOI
出版ステータスPublished - 03-2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬理学(医学)
  • 感染症

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