Ocular and systemic distribution, and excretion of radioactivity following topical ocular administration of 14C‐TG100801 to pigmented rabbits

Abstract Purpose: To determine the ocular distribution, systemic exposure, and routes of excretion of single 0.44 mg/eye topical ocular doses of 14C‐TG100801 to pigmented rabbits. Methods: Dutch Belted rabbits received single topical ocular doses of 14C‐TG100801. One group received bilateral doses; urine and feces were analyzed by LSC. Two groups received unilateral doses and were analyzed by quantitative autoradiography. Transverse and sagittal sections, respectively, were used to determine ocular and whole‐body distribution. Results: There was considerable local absorption of 14C‐TG100801 into ocular tissues and no appreciable systemic or contralateral eye exposure. Highest levels were in tissues of the anterior globe and radioactivity was translocated to the posterior globe (posterior sclera, choroid, and retina) for up to 96 hours. Little or no radioactivity was detected in the iris, ciliary body, lens, vitreous humor, or optic nerve head. In the whole body, radioactivity was primarily confined to the contents of the gastrointestinal tract. The primary route of elimination of was via feces. Conclusions: The results of this investigation demonstrate the efficiency of topical ocular instillation of TG100801 for treatment of local tissue while circumventing systemic exposure; there was considerable local ocular absorption of 14C TG100801 into the anterior globe, progressing to the tissues of the posterior globe (posterior sclera, choroid, and retina). Radioactivity in the posterior globe was likely absorbed and translocated to this location because it is beyond the conjunctival fornix. There was no appreciable systemic or contralateral eye exposure and radioactivity was primarily excreted via the feces.