title: Chlorothiazide is a substrate for the human uptake transporters OAT1 and OAT3.
abstract: The thiazide diuretic chlorothiazide is poorly metabolized, and is predominantly excreted via the kidneys. We have previously shown that chlorothiazide is transported by ATP-binding cassette transporter G2, suggesting a potential role for this transporter in apical efflux of chlorothiazide in the kidney. However, because of the poor passive permeability of the drug, it is likely that uptake transporters on the basolateral membrane are also involved to facilitate vectorial transport in the renal proximal tubule. Two suggested candidate transporters for this role are the human organic anion transporters, OAT1 and OAT3. By using mammalian cells stably expressing these transporters, we have demonstrated OAT1- and OAT3-dependent uptake of chlorothiazide with Michaelis constant values of 14.5 and 37.6 µM, respectively. Furthermore, we have found that probenecid, furosemide, and diclofenac inhibit chlorothiazide transport by OAT1 and OAT3, of which the probenecide-mediated inhibition may be of clinical importance. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1683-1687, 2013.
authors: Solvo Biotechnology, Budaörs 2040, Hungary.
authors: Viktória
authors: V
authors: Juhász
authors: Erzsébet
authors: E
authors: Beéry
authors: Zoltán
authors: Z
authors: Nagy
authors: Annamária
authors: A
authors: Bui
authors: Eva
authors: E
authors: Molnár
authors: Joseph Krisjanis
authors: JK
authors: Zolnerciks
authors: Rémi
authors: R
authors: Magnan
authors: Márton
authors: M
authors: Jani
authors: Peter
authors: P
authors: Krajcsi
mesh_terms: D000818:Animals; D016466:CHO Cells; D002740:Chlorothiazide / Q000378:metabolism*; D006224:Cricetinae; D004232:Diuretics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*
chemical_list: D004232:Diuretics; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D002740:Chlorothiazide