PHOTOSENSITIZATION BY NORFLOXACIN IS A FUNCTION OF PH

Norfloxacin is a fluoroquinolone (FQ) antibiotic that has been reporte d to cause cutaneous photosensitivity in animals and occasionally in h umans. We have studied the fluorescence and singlet oxygen (O-I(2))-ge nerating properties of norfloxacin, Upon UV excitation the drug fluore sces in water, and the relative intensities of two major fluorescence bands at ca 420 and 450 mm are affected by pH. The overall quantum yie ld 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, t hen gradually decreasing to 0.01 at pH 10, The changes in Phi(F) are a ccompanied by changes in fluorescence lifetime from 0.6 ns at pH 1 to 1.8 ns at pH 4. Norfloxacin exhibits phosphorescence in low temperatur e glasses, The formation of a triplet state at room temperature is als o suggested by O-I(2) phosphorescence in aerobic D2O. This phosphoresc ence is ''self-quenched'' by norfloxacin itself with an efficiency tha t is pH dependent: k(q) 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 a lkaline D2O solutions, This quenching causes the observed O-I(2), prod uction by norfloxacin (0.1 mM) to show a maximum at around pH 8-9, How ever, after correction for self-quenching, the quantum yield of O-I(2) , production (Phi(50)), measured by using perinaphthenone as a standar d, yielded the following values: Phi(50), is about 0.07 in 0.2 1Y DCI solution, 0.08 at pH 7.5 and then increases smoothly to similar to 0.2 in 0.1 M NaOD solution, The relatively high, unquenched O-I(2) produc tion at physiological pH 7.4 (Phi(50) similar to 0.08) suggests that O -I(2) reactions mag play an important role in the cutaneous phototoxic ity of norfloxacin and other FQ antibiotics.