Photosensitization by norfloxacin is a function of pH

Norfloxacin is a fluoroquinolone (FQ) antibiotic that has been reported to cause cutaneous photosensitivity in animals and occasionally in humans. We have studied the fluorescence and singlet oxygen (1O2)-generating properties of norfloxacin. Upon UV excitation the drug fluoresces in water, and the relative intensities of two major fluorescence bands at ca 420 and 450 nm are affected by pH. The overall quantum yield of fluorescence (phi F) is also strongly pH dependent: phi F is low in 0.2 N HCl solution (0.2), increasing steeply to 0.12 at pH 4, then gradually decreasing to 0.01 at pH 10. The changes in phi F are accompanied by changes in fluorescence lifetime from 0.6 ns at pH 1 to 1.8 ns at pH 4. Norfloxacin exhibits phosphorescence in low temperature glasses. The formation of a triplet state at room temperature is also suggested by 1O2 phosphorescence in aerobic D2O. This phosphorescence is "self-quenched" by norfloxacin itself with an efficiency that is pH dependent: kq is 7.9 x 10(6) M-1 s-1 at pD 4, decreases to 1.9 x 10(6) M-1 s-1 at pD 7.5 but then increases about 20-fold in alkaline D2O solutions. This quenching causes the observed 1O2 production by norfloxacin (0.1 mM) to show a maximum at around pH 8-9. However, after correction for self-quenching, the quantum yield of 1O2 production (phi 50)y measured by using perinaphthenone as a standard, yielded the following values: phi s0 is about 0.07 in 0.2 N DCI solution, 0.08 at pH 7.5 and then increases smoothly to approximately 0.2 in 0.1 M NaOD solution. The relatively high, unquenched 1O2 production at physiological pH 7.4 (phi s0 approximately 0.08) suggests that 1O2 reactions may play an important role in the cutaneous phototoxicity of norfloxacin and other FQ antibiotics.