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In vitro Transporter Screens to Investigate Uremic Solute‐Drugs Interaction
Author(s) -
Chang ShihYu,
Chapron Alenka,
Imaoka Tomoki Imaoka,
Yeung Catherine K
Publication year - 2019
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.2019.33.1_supplement.507.1
Subject(s) - transporter , pharmacology , efflux , chemistry , organic cation transport proteins , uremia , organic anion transporter 1 , multidrug resistance associated protein 2 , hippuric acid , biochemistry , atp binding cassette transporter , biology , endocrinology , gene , urine
Renal tubule secretion via transporter proteins plays a critical role in the renal clearance of drugs and endogenous compounds. We hypothesize that competition between accumulating uremic solutes and drugs for proximal tubule transport results in unpredictable drug exposure in people with kidney disease. The goal of this study was to characterize the potential of prominent uremic solutes, including hippuric acid (HA), indoxyl sulfate (IS), p‐cresol sulfate (pCS) and trimethylamine N‐oxide (TMAO), to inhibit renal tubule transport. We used penciclovir (PEN), oseltamivir carboxylate (OST) and tenofovir (TEN) in our study as model transporter substrates. We conducted systemic screens of transporter inhibition using in vitro assays, including uptake (overexpressed cell lines) and efflux (in‐side out vesicle membranes) transporters, to investigate whether uremic solutes and model drugs are potential inhibitors/substrates of renal uptake and efflux transporters involved in tubular secretion (OAT1/2/3, MRP2/4, MATE1/2K, P‐gp, BCRP). This systematic study of uremic solute ‐ drug interaction demonstrated that some uremic solutes and drugs (PEN and TEN) might compete and inhibit uptake transporters via OATs and efflux via MRPs transporters. A clearer understanding of the interactions between drugs and uremic solutes may lead to personalized approaches for the selection and dosing of medications in people with kidney disease. Support or Funding Information 5 R01 GM 121354‐02 UREMIA TRANSPORT This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .