Relationship between Concentrations and Phototoxicity of Fluoroquinolones in Mice

흰쥐에서의 Fluoroquinolone계 항균제 농도와 광독성의 상관관계

The fluoroquinolones have been reported to cause, although at low frequency, severe phototoxicity which is due to singlet oxygen produced by ultraviolet-A (UVA; 320-400 nm) exposure. The objective of this study was to evaluate the phototoxicity based on plasma and tissue concentrations of commonly prescribed fluoroquinolones; lomefloxacin (LFLX), enoxacin (ENX), ofloxacin (OFLX), and ciprofloxacin (CPFX). The phototoxic potentials were investigated by measuring increments in ear thickness, 24 hrs after these fluoroquinolones were orally administered to Balb/c mice, which they were exposed to UVA 17.5 J/$\textrm{cm}^2$ for 2 hrs following drug administration. The fifty percent ear thickness increment-inducing doses ($ETID_{50}$), determined by single ascending dosing of each fluoroquinolone to mice, were calculated to be 50(LMFX), 250(ENX), 770(OFLX), 1100(CPFX) mg/kg. Post the administration of ETID$_{50}$, drug concentrations in plasma and ear tissue were measured at specified times and phototoxicities were quantified. Both peak plasma ($\mu\textrm{g}$/ml) and ear tissue ($\mu\textrm{g}$/g) concentrations were summarized as follows; 7.3/1.4 for LMFX, 15.0/1.6 for ENX, 90.1/18.4 for OFLX and 87.2/3.7 for CPFX. The degree of photo toxicity was more relevant to plasma concentrations than tissue concentrations. In order to assess the effect of irradiation time after drug administration on phototoxicity, the 2 hr UVA irradiation was given at 0, 1, 2, 3, and 5 hr after administering $ETID_{50}$, respectively and photo toxicities were evaluated. The shorter inteval between dosing and UVA exposure was, the higher risk of phototoxicity was produced.d.