Absorption, distribution and excretion of 14C-levofloxacin after single oral administration in albino and pigmented rats: binding characteristics of levofloxacin-related radioactivity to melanin in vivo.

After single oral administration of (14)C-levofloxacin at a dose of 20 mg kg(-1) under non-fasting conditions, the absorption, distribution and excretion of radioactivity were studied in albino and pigmented rats. Good penetration of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there were no quantitative differences in the distribution of radioactivity between albino and pigmented rats except for melanin-containing tissues such as the uveal tract of eyes and hair follicles. There was selective and strong binding of drug-related radioactivity to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value (C(max)) of 26.33 +/- 0.75 microg eq. g(-1) at 24 h after dosing and declined slowly with a terminal half-life of 468.1 h (19.5 days). The uveal tract concentration at 12 weeks was 0.73+/- 0.12 microg eq. g(-1), which is c. 1/36 of C(max). The AUC(0- infinity ) for the uveal tract was 12.58 mg h(-1) g(-1). The uveal tracts separated from one eye of each rat were extracted with 0.067 M phosphate buffer (pH 7.4) and 1M HCl/EtOH (30:70), successively. In pigmented rats, approximately 85-48% of radioactivity bound to the uveal tract was released from the tissue by the washing procedures. Most of the eluted radioactivity was released with 1M HCl/EtOH (30:70), indicating that the binding to melanin is reversible, and hydrophobic and electrostatic interactions play an important role in the binding of levofloxacin and/or its metabolites with melanin-containing ocular tissues. Only unchanged drug was detected in the extracts of the uveal tracts. The concentrations and half-life of radioactivity in the uveal tract after dosing of (14)C-levofloxacin were found to be much lower and shorter than those after dosing of (14)C-chloroquine. It is unlikely that levofloxacin causes toxicity because of its much lower affinity to melanin-containing ocular tissues and shorter duration of therapy compared to chloroquine.