title: Renal excretion of emtricitabine I: effects of organic anion, organic cation, and nucleoside transport inhibitors on emtricitabine excretion.
abstract: The excretion of emtricitabine (FTC) was characterized using isolated perfused rat kidney (IPK) model. Studies were performed to assess the dose-linearity of FTC excretion, to evaluate the effect of inhibitors of organic anion (probenecid, PBC), organic cation (tetraethylammonium, TEA; cimetidine, CMD) and nucleoside (uridine, URD) transport systems on FTC excretion, and to determine the potential interaction between FTC and trimethoprim (TMP). FTC excretion was studied over a range of doses (80-1600 microg), targeting concentrations encompassing the therapeutic range of FTC (1-20 microg/mL). FTC (2 microg/mL) was also coperfused with PBC (500 microM), TEA (500 microM), CMD (2 mM), URD (500 microM), and TMP (13.7 microM). FTC dose-linearity studies revealed that excretion parameters were not significantly different among dosing groups. Of the transport inhibitors tested, FTC XR decreased more than twofold in the presence of CMD (0.32 +/- 0.099). PBC, TEA, and URD had no observed effect on FTC excretion. TMP coadministration significantly inhibited FTC excretion (XR = 0.43 +/- 0.052). The results suggest that FTC renal transport is likely mediated by a CMD-sensitive organic cation transporter (OCT) in the kidney. TMP may inhibit the renal excretion of FTC when the two compounds are coadministered in vivo.
authors: Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 DeKalb Ave., Brooklyn, New York 11201, USA.
authors: Tomoko
authors: T
authors: Nakatani-Freshwater
authors: David R
authors: DR
authors: Taft
mesh_terms: D000818:Animals; D000838:Anions; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001692:Biological Transport; D002412:Cations; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068679:Emtricitabine; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009705:Nucleosides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000838:Anions; D000998:Antiviral Agents; D002412:Cations; D009705:Nucleosides; D003841:Deoxycytidine; D000068679:Emtricitabine