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

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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℃ and pH 7.4. In the case of ofloxacin, however, the erythrocytes took up ofloxacin in a concentration dependent manner at 20℃ and pH 7.4,with a maximum rate (J_<max>) of 28.8±0.98 pmol/10^6 cells/s and a Michaelis constant (K_t) of 0.92±0.15 mM. An increase in the medium osmolarity caused a decrease in the [^<14>C] lomefloxacin uptake, indicating that the drug is transported into the intracellular space of erythrocytes. The uptake of [^<14>C] 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 [^<14>C] lomefloxacin was competitively inhibited by a water-soluble vitamin, nicotinic acid, with an inhibition constant (K_i) 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.
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