Phototoxicity of Quinolones: Measurement by UV-A Inhibition of Concanavalin A-Stimulated Lymphocyte Mitogenic Response

Abstract

Phototoxicity of ten quinolones was measured by inhibition of concanavalin A-stimulated mitogenesis (measured by [3H]-thymidine uptake) of guinea pig splenocytes after UV-A irradiation in the presence of drug. At a drug concentration of 2.5μg/ml and a radiation dose of 3.9J/cm2, inhibition rates (expressed as percentage of uptake, without irradiation) were: lomefloxacin (LFLX), 51%; fleroxacin (FLRX), 34%; ciprofloxacin (CPFX) and enoxacin (ENX), 27%; norfloxacin (NFLX), 25%; ofloxacin (OFLX), 19%; piromidic acid (PA), 13% tosufloxacin (TFLX), 12%; pipemidic acid (PPA), 11%; and levofloxacin (LVFX, an optical isomer of OFLX), 8%. At a concentration, of 25 μg/ml, on the other hand the phototoxic activity of quinolones decreased in the order LFLX, CPFX, ENX, FLRX>NFLX>LVFX, PA, OFLX>PPA. These results suggest that LFLX, with a fluorine attached to the 8 position, is strongly photoxic, although it shows low cytotoxicity (measured by inhibition of incorporation in the dark), against splenocytes. UV-A irradiation of solutions of LFLX and FLRX blue-shifted the absorption maximum from 280 nm to 270 nm and decreased the optical density between 325 and 340 nm. Although CPFX, ENX, NFLX, OFLX, LVFX and PA also showed optical density decreases at 260–290 nm and 325–350 nm, the maximal absorption did not shift. There were no changes in the absorption spectra of PPA and TFLX even after UV-A irradiation at a dose of 7.8J/cm2. Thus, quinolones phototoxicity and the spectral changes produced by UV-A irradiation appear to be related.