Grepafloxacin Concentration in Ocular Tissues after Intravenous Infusion in Rabbits with Intraocular Inflammation

Abstract

Purpose: To determine the penetration of grepafloxacin into ocular tissues during experimental ocular inflammation. Methods: 10 albino and 10 pigmented rabbits underwent a continuous intravenous infusion of the drug 24 h after injecting Salmonella typhimurium toxin intravitreously, creating ocular inflammation. The animals were killed and grepafloxacin levels were determined in plasma and ocular tissues using high performance liquid chromatography. Results: Grepafloxacin levels achieved a steady-state plasma concentration of 1.5 µg/ml. The drug diffused more towards vascularized tissues (chorioretina and iris) in both albino and pigmented rabbits with a tissue/serum ratio higher than 1. Grepafloxacin showed more affinity to pigmented tissue, rising levels of 40,000–50,000 ng/g in the chorioretina and iris in pigmented animals. After inflammation, grepafloxacin intraocular penetration increased in albino animals with levels exceeding the minimum inhibitory concentration for the most common ocular pathogens. Conclusion: Grepafloxacin intraocular penetration is higher in pigmented tissues. Ocular inflammation increases the drug penetration into the vitreous.

The Vitreous Humor As a Barrier to Nanoparticle Distribution

“…Intravenous infusion of Salmonella typhimurium toxin to the rabbit produced an increased absorption of grepafloxacin into the vitreous humor in albino rabbits from the plasma. 38 The decrease in barrier function also markedly increased iris and ciliary body levels in the Gigante de Españ a species (the drug is highly melanin bound). In the pig, unilateral vitrectomy disturbs the retinal-blood barrier and, 1 month after the procedure, fluorescein given intravenously penetrates the vitreous more readily giving a markedly higher area under the curve.…”