Clearance of S-(3-amino-2-hydroxypropyl) phosphorothioate (WR-77913) in rats

Complications of radiotherapy in the treatment of retinal and choroidal neoplastic diseases include cataract formation, radiation retinopathy, neovascular glaucoma, cystoid macular edema, and subretinal neovascularization. These side effects may be minimized by the use of compounds known to have a protective effect on normal ocular tissues without impeding the benefits of therapy. Phosphorothioates, first developed under the Antiradiation Drug Development Program of the U.S. Army Medical Research and Development Command, have been reported to protect normal tissues during radiation therapy in a variety of animal models. One of the phosphorothioates, WR-77913 (S-[3-amino-2-hydroxylpropyl] phosphorothioate) was found to inhibit cataract formation in rats after radiation exposure. To test the efficacy of WR-77913 in the retina, we established a high-pressure liquid chromatography method to measure the levels of dephosphorylated WR-77913 and studied the drug's clearance from the lens, retina, blood, kidney, and liver in rats.