title: Interaction of ofloxacin with organic cation transport system in rat renal brush-border membranes.
abstract: Ofloxacin, a pyridonecarboxylic acid derivative, was examined for its effects on the transport of tetraethylammonium (cation), cephalexin and cephradine (zwitterions), p-aminohippurate (anion) and D-glucose in brush-border membrane vesicles isolated from rat renal cortex. The initial uptake of tetraethylammonium in the presence or absence of an outward H+ gradient was inhibited by ofloxacin in a dose-dependent manner, although the equilibrium value of tetraethylammonium uptake was not affected. This inhibition occurred in a competitive manner (Ki = 0.11 mM). Ofloxacin also inhibited the initial uptake of cephalexin and cephradine, which can be transported via the H+/organic cation antiport system in renal brush-border membranes. In contrast, ofloxacin had no effect on p-aminohippurate. These data suggest that ofloxacin interacts with the organic cation transport system in renal brush-border membranes, and this system may play an important role in the tubular secretion of ofloxacin.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okano
authors.forename: H
authors.initials: H
authors.lastname: Maegawa
authors.forename: K
authors.initials: K
authors.lastname: Inui
authors.forename: R
authors.initials: R
authors.lastname: Hori
mesh_terms: D000818:Animals; D002506:Cephalexin / Q000493:pharmacokinetics*; D002515:Cephradine / Q000493:pharmacokinetics*; D005947:Glucose / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007672:Kidney Cortex / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000378:metabolism*; D015242:Ofloxacin / Q000494:pharmacology*; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000493:pharmacokinetics*; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
chemical_list: D011522:Protons; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D015242:Ofloxacin; D002515:Cephradine; D005947:Glucose; D002506:Cephalexin; D010130:p-Aminohippuric Acid