Relationship between Concentrations and Phototoxicity of Fluoroquinolones in Mice

흰쥐에서의 Fluoroquinolone계 항균제 농도와 광독성의 상관관계

  • Published : 2002.12.01

Abstract

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.

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References

  1. Appelbaum, P.C. and Hunter, P.A. (2000) The fluoroquinolone antibacterials: past, Present, and future perspectives. International Journal of Antimicrobial agents, 16, 5-15 https://doi.org/10.1016/S0924-8579(00)00192-8
  2. Ball, P. (2000) Quinolone generations: natural history or natural selection? Journal of Antimicrobial Chemotherapy, 46, 17-24
  3. Cho, Y.H., Kim, T.H., Park, H.B. et al. (1995) Evaluation of the phototoxic potential of some quinolone antibiotics. Korean Journal of Dermatoloey, 33, 1021-1028
  4. Cole, C., Sambuco, C., Forbes, P. et al. (1984) Response to ultraviolet radiation: Ear swelling in hairless micc. Photodermatotogy, 1, 114
  5. Cole, C., Davies, R., Forbes, P, et al. (1983) Comparison of action spectrum for acutc cutancous response to ultraviolet radiation: Man and albino hairlcss mouse. Photochem Photobiol, 37, 623 https://doi.org/10.1111/j.1751-1097.1983.tb04531.x
  6. Domagala, J.M. (1994) Structure activity and structure side effect relationships for the quinolone antibacterials. Journal of Antimicrobial Chemotherapy, 33, 685-706 https://doi.org/10.1093/jac/33.4.685
  7. Fugita, H. and Matsuo, I. (1994) Jn vitro phototoxic activities of new quinolone antibacterial agents: lipid peroxidative potentials. Photodermatol. Photoimmunol. Photomed., 10, 202-205
  8. Grasela, T.H., Scbentag, J.J., and Sedman, A.J. et al. (1989) Inhibition of enoxacin absorption by antacids or ranitidine. Antimicrobial Agents and Chemotherapy, 33, 615-617 https://doi.org/10.1128/AAC.33.5.615
  9. Ikai, K., Danno, K., and Horia, T. et al. (1986) Ear swellmg in response to UVB iiradiation. Arch. Dermatol. Res., 278, 445
  10. Jill, E.A. (1993) Drug induced photosensitivity. Clinical Pharmacy, 12, 580-587
  11. Kiyoshi, M. and Masahiko, M. et al. (1993) Reduced photoloxicity of a fluoroquinolonc antibacterial agent with a methoxy group at fhe 8 position in micc irradiated with long wavelength UV light. Antimicrobial Agents and Chemotherapy, 37, 2217-2223 https://doi.org/10.1128/AAC.37.10.2217
  12. Lee, H.S., Kim, T.H., and Park, K.B. et al. (1994) Evaluation of the phototoxic potential of the diuretic agents by the photohcmolysis test and the Candida albicans test. Korean Journal of Dermatotogy, 32, 640-648
  13. Mizuno, A., Uematsu, T., and Nakashirma, M. (1994) Simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair by bigh performance liquid chromatography and fluorescence detection. Journal of Chromato graphv, B653, 187-193
  14. Mignot, A. and Lefebvre, M.A. et al. (1988) High performance liquid chromatographic determiination of ofloxacin in plasma and urine. Journal of Chromatography, 430, 192-197 https://doi.org/10.1016/S0378-4347(00)83152-7
  15. Nilsson, R., Maurer, T., and Redmond, N. (1993) A standard protocol for phototoxicity testing: Results from an interlaboratory study. Contact Dermatitis, 28, 283-290
  16. Norrby, S.R. and Lietman, P.S. (1993) Safety and tolcrability of fluoroquinolones. Drugs 45(supp1. 3), 59-64 https://doi.org/10.2165/00003495-199300453-00012
  17. Rubinstein, E. (2001) Histoiy of qumolones and their sidc effects. Chemotherapy, 47(supp1. 3), 3-8
  18. Shimoda, K., Yoshida, M., Wagai, N., Takayama S., and Kato, M. (1993) Phototoxic lesions induced by quinolonc antibacterial agents in auricular skin and retina of albino mice. Toxicol. Patholo., 21, 554-561 https://doi.org/10.1177/019262339302100606
  19. Shosuke, K. and Yusuke, H. (2001) Sequence-specific DNA damage induced by UVA radiation in the presence of endogenous and exogenous photosensitizers. Curr Probl Dermatol., 29, 74-82
  20. Skerrow, C.J. and Skerrow, D. (1985) A survey of methods for die isolation and fractionation of epidermal tissue and cells. Methods in Skin Research, 609-643
  21. Takayama, S., Hirohashi, M., Kato, M., and Shimada, H., (1995) Toxicity of quinolone antimicrobial agents. Jornnal of Toxicology and Environmental Health, 45, 1-45
  22. Wagai, N. and Tawara, K. (1991). Quinolonc antibacterial agent induced cutaneous phototoxicity: ear swelling rcaction in Ba1b/c mice. Toxicol. Letters, 58, 215-223 https://doi.org/10.1016/0378-4274(91)90176-7
  23. Wagai, N., Yamaguchi F., Sekiguchi, M., and Tawara, K. (1990b) Phototoxic potential of quinolone antibacterial agenls in Balb/c mice. Toxicol. Letters, 54, 299-308 https://doi.org/10.1016/0378-4274(90)90197-T
  24. Wagai, N., Yamaguchi, F., Tawara, K., and Onodem, T. (1990a) Studies on experimental conditions for detection phototoxic potentials of drugs in Ba1b/c mice. J. Toxicol. Sci., 14, 197-204
  25. Wagai, N. and Tawara, K. (1992) Possible direct role of reactive oxygens in the cause of cutenous phototoxicity induced by five quinolones in mice. Arch Toxicol., 66, 392-397 https://doi.org/10.1007/BF02035128
  26. Wolfson, J.S. and Hooper, D.C. (1991) Overview of fluoroquinolone safely. The American Journal of Medicine, 91 (suppl. 6A), 153S-158S https://doi.org/10.1016/0002-9343(91)90330-Z
  27. Yeo, U.C. and Kim, K.H. et al. (1989) Inflammatory skin response to ultraviolet radiation: ear swelling response in C57BL mouse. Korean Journal of Dermatology, 27, 650-654