Transport of the New Quinolone Antibacterial Agents of Lomefloxacin and Ofloxacin by Rat Erythrocytes, and Its Relation to the Nicotinic Acid Transport System

Matheus Timbul Simanjuntak, Hitoshi Sato, Ikumi Tamai, Tetsuya Terasaki, Akira Tsuji

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15 Citations (Scopus)

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 °C and pH 7.4. In the case of ofloxacin, however, the erythrocytes took up ofloxacin in a concentration dependent manner at 20 °C and pH 7.4, with a maximum rate (Jmax) of 28.8±0.98 pmol/106 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 (KA) of 16.1 mM, but not inhibited by 10 mM of L-alanine, glucose, p-aminohippuric acid (PAH), N-methyl-nicotinamide (NMN) or tetraethylammo-nium 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.

Original languageEnglish
Pages (from-to)475-481
Number of pages7
Journaljournal of pharmacobio-dynamics
Volume14
Issue number8
DOIs
Publication statusPublished - 1991 Jan

Keywords

  • carrier mediated transport
  • erythrocyte uptake
  • lomefloxacin (NY-198)
  • nicotinic acid
  • ofloxacin
  • quinolones

ASJC Scopus subject areas

  • Pharmacology

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