Comparative assessment of ocular tissue distribution of drug-related radioactivity after chronic oral administration of 14C-level of loxacin and 14C-chloroquine in pigmented rats

Fluoroquinolones have been reported to have a high affinity for melanin. The ocular tissue distribution and accumulation of radioactivity was compared after repeated oral administration of C-14-levofloxacin and C-14-chloroquine at daily doses of 20 mg (0.054 mmol) kg(-1) and 28 mg (0.054 mmol) kg(-1), respectively, in pigmented rats for 84 days. The mean serum level at 24 h following each dose of 14C-levofloxacin was almost constant in the range of 0.33-0.45 nmol equiv mL(-1) after the 14(th) dose and thereafter. The melanin-containing ocular tissue!, such as iris ciliary body and stratum pigment chorioides sclera, showed a much higher concentration of radioactivity than other non-pigmented ocular tissues. The respective concentration in iris ciliary body and stratum pigment chorioides sclera after the 1(st) dose was 126.47 and 74.91 nmol equiv g(-1), and gradually increased with increasing dose number, reaching 1261.81 and 447.45 nmol equiv g(-1) after the 84(th) dose, which was ca. 10 and 6 times higher, respectively, than after the 1(st) dose. The mean serum level following each dose of C-14-chloroquine was almost constant in the range 0.51-0.87 nmol equiv mL(-1) after the 7(th) dose and thereafter. The respective concentration in iris ciliary body and stratum pigment chorioides sclera after the 1(st) dose was 572.10 and 709.41 nmol equiv g(-1), and gradually increased with increasing dose number, reaching 33317.92 and 12322.90 nmol equiv g(-1) after the 84(th) dose, which was ca. 58 and 17 times higher, respectively, than after the 1(st) dose. The concentration in aqueous humour, cornea, lens, vitreous body and retina after the 84(th) close was 1.84, 6.33, 0.48, 5.60 and 11.42 nmol equiv g(-1) for C-14-levofloxacin and 18.84, 264.99, 27.26, 158.43 and 1020.89 nmol equiv g-1 for 14 C-chloroquine (ca. 10, 42, 57, 28 and 89 times higher, respectively, than for C-14-levofloxacin). Especially, the concentration in the retina was markedly higher after 14 C-chloroquine administration than after C-14-levofloxacin administration. The concentration and the extent of accumulation of radioactivity not only in melanin-containing ocular tissues but also in other nonpigmented ocular tissues, such as retina, after chronic oral administration of C-14-levofloxacin once daily for 84 days were much lower than those after multiple dosing with C-14-chloroquine under the same conditions. These results indicate that levofloxacin would have a much lower risk for ocular toxicity than chloroquine after chronic dosing.