Matsui Ryutaro, Hattori Ryutaro, Usami Youhei, Koyama Masumi, Hirayama Yuki, Matsuba Emi, Hashimoto Yukiya
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-1094, Japan.
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-1094, Japan.
Drug Metab Pharmacokinet. 2018 Feb;33(1):96-102. doi: 10.1016/j.dmpk.2017.11.313. Epub 2017 Dec 5.
We have recently found an H/quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H/lipophilic cation antiport system is expressed in porcine LLC-PK cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H/lipophilic cation antiport system is expressed in the apical membrane of LLC-PK cells. Moreover, the H/lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats.
