title: Fluoroquinolone disposition: identification of the contribution of renal secretory and reabsorptive drug transporters.
abstract: BACKGROUND
  Fluoroquinolones (FQs) exist as charged molecules in blood and urine making their absorption, distribution, and elimination likely to be influenced by active transport mechanisms. Greater understanding of in vivo FQ clearance mechanisms should help improve the predictability of drug-drug interactions, enhance the clinical safety and efficacy, and aid future novel drug design strategies.
  
  
  METHODS
  The authors present an overview of FQ development and associated drug-drug interactions, followed by systematic quantitative review of the physicochemical and in vivo pharmacokinetic properties for 15 representative FQs using historical clinical literature. These results were correlated with in vitro studies implicating drug transporters in FQ clearance to link clinical and in vitro evidence supporting the contribution of drug transport mechanisms to FQ disposition. Specific transporters likely to handle FQs in human renal proximal tubule cells are also identified.
  
  
  CONCLUSIONS
  Renal handling, that is, tubular secretion and reabsorption, appears to be the main determinant of FQ plasma half-life, clinical duration of action, and drug-drug interactions. Due to their zwitterionic nature, FQs are likely to interact with organic anion and cation transporters within the solute carrier (SLC) superfamily, including OAT1, OAT3, OCT2, OCTN1, OCTN2, MATE1, and MATE2. The ATP-binding cassette (ABC) transporters MDR1, MRP2, MRP4, and BCRP also may interact with FQs.
authors.affiliation: Virginia Commonwealth University, School of Pharmacy, Department of Pharmaceutics, Richmond, VA 23298, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Mulgaonkar
authors.forename: Jurgen
authors.initials: J
authors.lastname: Venitz
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Sweet
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D001693:Biological Transport, Active; D015195:Drug Design; D004347:Drug Interactions; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D024841:Fluoroquinolones; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent