Intraocular pharmacokinetics of norfloxacin (NFLX) in pigmented animals

Abstract

The intraocular pharmacokinetics of norfloxacin (NFLX) after 2 weeks of consecutive oral administration or instillation of [¹⁴C]-NFLX in beagle dogs and pigmented rabbits were studied for 6 months. The following results were obtained.
1) The concentration of radioactivity in the choroid and pigment epithelium (choroidpigment epithelium) of dogs was 433 μg eq./g at 24 hours, 276 μg eq./g at 1 month, and 89.6 μg eq./g at 6 months after the last 30 mg/kg administration of [¹⁴C]-NFLX.
2) The concentration in choroid-pigment epithelium of rabbit was about 90.3 μg eq./g at 24 hours after the last 50 mg/kg administration of [¹⁴C]-NFLX
3) Concentrations in non-pigmented tissues were lower than the serum level.
4) In the case of instillation with 50 μl of 0.3%[¹⁴C]-NFLX at 5 times/day for 2 weeks, the concentration in the iris-ciliary body and the choroid-pigment epithelium of dogs were 6.74 and 2.03 μg eq./g, respectively, at 24 hours after the last application, and these radioactivities decreased slowly thereafter.
5) Microautoradiography showed the localization of radioactivity only in the uvea, without showing diffusion into the retina.
These results indicate that NFLX has an affinity for melanin, and results in a high accumulation and retarded residue in the melanotic ocular tissues. Fluoroquinolones are known to have a strong affinity for melanin. Lomefloxacin and levofloxacin are reported to accumulate in the uvea of beagle dogs at the level of 1, 200 μg/g. In the monkey, fluoroquinolone accumulation of 138-300 μg/g is reported. Based on these findings, long-term use of fluoroquinolones should be considered in order to avoid melanin disorder.