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The Clinical Implication of Compounds which could induce the function of human organic cation transporter 2 (hOCT2), while inhibit the function of human Multidrug and Toxin Extrusion Proteins 1 (hMATE1)
Author(s) -
YANG HONG,
Guo Dong,
Shu Yan
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.693.7
Subject(s) - organic cation transport proteins , transporter , function (biology) , drug , pharmacology , metformin , imatinib , physiologically based pharmacokinetic modelling , chemistry , in vivo , downregulation and upregulation , drug delivery , pharmacokinetics , medicine , cancer research , microbiology and biotechnology , biology , biochemistry , gene , endocrinology , myeloid leukemia , organic chemistry , diabetes mellitus
The human organic cation transporter 2 and human multidrug and toxin extrusion protein 1 (hOCT2/hMATE1) transport system is a pair of transporter proteins highly expressed at the basolateral and apical membrane of renal proximal tubules respectively. They function collaboratively to facilitate elimination of a variety of compounds into urine, thus playing a crucial role in drug disposition and response. Preliminary data from our lab showed that acute exposure (20 minutes) of Cd 2+ could significantly upregulate the activities of human hOCT2, while inhibit the function of hMATE1, both in a dose‐dependent manner (Fig. 1A&1B). Beside Cd 2+ , we identified imatinib, an anticancer drug, could induce the function of hOCT2 while inhibit the function of hMATE1 (Fig. 2). In vivo study also showed that pre‐treatment of imatinib could significantly increase the accumulation of metformin in mice kidney while had no impact on the plasma exposure of metformin (Fig. 3A&3B). It implicated that the index of plasma drug exposure will not be able to correctly reflect drug‐drug interaction when a drug could induce hOCT2 while inhibit hMATE1 at the same time, which potentially could cause significant drug accumulation in kidney tubular cells. Support or Funding Information NIH: R01GM099742FDA: U01FD004320 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .