K. Marutani et al., REDUCED PHOTOTOXICITY OF A FLUOROQUINOLONE ANTIBACTERIAL AGENT WITH AMETHOXY GROUP AT THE 8-POSITION IN MICE IRRADIATED WITH LONG-WAVELENGTH UV-LIGHT, Antimicrobial agents and chemotherapy, 37(10), 1993, pp. 2217-2223
A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy g
roup was substituted at the 8 position of the quinoline nucleus, was v
ery stable under irradiation with long-wave UV light (UVA). Derivative
s, a fluoroquinolone with no substitution (the 8-H analog) and one in
which a fluorine was substituted (the 8-F analog), were degraded in th
eir solutions by the UVA irradiation. The phototoxic inducibility by t
hese derivatives was further studied in a murine model. When mice were
dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body weight, the
maximum dose given, and exposed to the UVA light, no inflammatory lesi
ons were observed in their ears. Ear redness was marked in mice given
more than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg
. Histopathological changes, edema, and infiltration of neutrophils we
re also observed microscopically in groups receiving the 8-H or 8-F an
alog but not in groups receiving Q-35 (8-OCH3). Similar inflammatory r
eactions were observed to occur in a dose-dependent manner with other
available fluoroquinolone antibacterial agents such as lomefloxacin, e
noxacin, norfloxacin, ciprofloxacin and ofloxacin. These results sugge
st that the introduction of a methoxy group at the 8 position of the q
uinolone nucleus is important for the reduction of phototoxicity.