Characterization of the carrier-mediated transport of levofloxacin, a fluoroquinolone antimicrobial agent, in rabbit cornea

The cornea presents a formidable barrier to drug penetration. The fluoroqui nolone levofloxacin, which is an effective antimicrobial agent, has the pot ential to be used in the topical treatment of ocular disease. Thus, we soug ht to characterize how levofloxacin penetrates the cornea. To perform this characterization, we measured the time dependent permeation of levofloxacin across the isolated rabbit cornea using a diffusion chamber, and compared it with antipyrine fluxes. Levofloxacin permeation into the receiver epithelial-side bathing solution (pH = 6.5) from the donor endothelial-side (pH = 7.4) reached 3.00 nmol cm( -2) cornea after 2 h, whereas in the opposite direction permeation was 1.89 nmol cm(-2) cornea. Based on the temperature-dependent effects on permeati on, the calculated energy of activation for permeation, E-a, was 31.3 kcal mol(-1) whereas E-a for antipyrine, a marker of diffusion, was 11.0 kcal mo l(-1). The transport of levofloxacin from epithelium to endothelium was con centration-dependent and had both a linear and saturable component. Evaluat ion of the kinetic parameters, J(max), apparent K-m and k(d) showed that th ey were 38.78 pmol min(-1) cm(-2), 3.83 mM and 0.0135 mu L min(-1) cm(-2) r espectively. These results, coupled with the fact that levofloxacin permeation reached a maximum value at pH 6.5, suggest that levofloxacin transport across the co rnea is carrier mediated. However, at present, it cannot be ascertained whe ther such a system is localized in either the corneal epithelial or the end othelial layer.