title: Transport of the new quinolone antibacterial agents of lomefloxacin and ofloxacin by rat erythrocytes, and its relation to the nicotinic acid transport system.
abstract: Transport mechanism of quinolonecarboxylic acid derivatives (quinolones), lomefloxacin and ofloxacin, in rat erythrocytes was investigated. The uptake of lomefloxacin by erythrocytes was apparently nonsaturable over the concentration range of 0.1-1.0 mM at 27 degrees C and pH 7.4. In the case of ofloxacin, however, the erythrocytes took up ofloxacin in a concentration dependent manner at 20 degrees C and pH 7.4, with a maximum rate (Jmax) of 28.8 +/- 0.98 pmol/10(6) cells/s and a Michaelis constant (Kt) of 0.92 +/- 0.15 mM. An increase in the medium osmolarity caused a decrease in the [14C]lomefloxacin uptake, indicating that the drug is transported into the intracellular space of erythrocytes. The uptake of [14C]lomefloxacin by the erythrocytes was independent of pH but increased above pH 6.0, and, moreover, was dependent on temperature with an activation energy of 16.6 kcal/mol. The uptake of [14C]lomefloxacin was competitively inhibited by a water-soluble vitamin, nicotinic acid, with an inhibition constant (Ki) of 16.1 mM, but not inhibited by 10 mM of L-alanine, glucose, p-aminohippuric acid (PAH), N-methyl-nicotinamide (NMN) or tetraethylammonium chloride (TEA). These lines of evidence suggest that the transport system of lomefloxacin and ofloxacin in rat erythrocytes is common with that of a water-soluble vitamin, nicotinic acid, to which quinolones are structurally analogous.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
authors.forename: M T
authors.initials: MT
authors.lastname: Simanjuntak
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: I
authors.initials: I
authors.lastname: Tamai
authors.forename: T
authors.initials: T
authors.lastname: Terasaki
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood* / Q000493:pharmacokinetics; D001693:Biological Transport, Active / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism*; D024841:Fluoroquinolones; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009525:Niacin / Q000378:metabolism* / Q000494:pharmacology; D015242:Ofloxacin / Q000097:blood* / Q000493:pharmacokinetics; D009994:Osmolar Concentration; D015363:Quinolones / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D009525:Niacin; D015242:Ofloxacin; C053091:lomefloxacin