Tissue Distribution and Relative Bioavailability of Ocularly–Administered Moxaverine–HCl

Abstract

Abstract: : Purpose:To study tissue distribution and relative bioavailability of topically–administered moxaverine–HCl to the rabbit eye. Introduction:In this study, we determined whether moxaverine–HCl (MOX), a drug not used in ophthalmic research before, could be delivered to sites of interest by topical application to the eye. Known characteristics of MOX include a high lipophilicity (log P 4.017). A good solubility in aqueous solvents is achieved by forming the HCl salt. Methods:Dutch–belted male pigmented rabbits were placed in a restrainer and 50 µL of an isotonic drug solution, spiked with 14C–moxaverine–HCl were applied to each eye. For the determination of ocular bioavailability after systemic administration, the same solution was given i.v.. At time points of 30 and 120 min, rabbits were sacrificed. From one eye, samples of aqueous humor and vitreous body were taken. The other eye was excised as a whole and dissected to yield the particular intraocular tissues. Tissues were lysed for 12 h, scintillation cocktail was added to the vials containing individual tissue lysates samples and the radioactivity was determined in a scintillation counter. Results:After topical administration, highest levels of MOX were found in conjunctiva, cornea and iris/ciliary body. Lens contained no measurable drug level. Concentrations within the retina were comparable to those obtained after systemic application. Plasma levels after topical dosing were lower compared to systemic dosing. Drug amounts in the sclera were lower following i.v. application at both 30 and 120 min. Conclusions:This study demonstrated the possibility of a targeted delivery of MOX to the posterior part of the eye by using eye drops. Concentrations in the retina were equal (30 min) or even higher (120 min) after topical administration, compared to i.v. application. Acknowledgements: Ms. Dorothea Groß and Dr. Klaus Eschmann (Ursapharm) are thanked for their support of this work.

Keywords: pump/barrier function • pharmacology • retina