Long-Acting Therapy of Viral Retinitis with (S)-1-(3-Hydroxy-2-Phosphonylmethoxypropyl) cytosine

Abstract

(S)-I-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency anti-herpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of experimental retinitis caused by preretinal herpes simplex virus (HSV-I) injection in rabbits. HPMPC (100 μg/O.1 mL) was intravitreally injected 10, IS, 21, 30, or 46 days before,concurrently,or 3, 5, or 7 days after viral inoculation. Ganciclovir (200 μg/O.1 mL) was intravitreally injected 3, 7, or 10 days before HSV-I inoculation, concurrent with viral inoculation, or 3, 5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected from retinitis for 15-21 days. Ganciclovir did not protect completely even if administered 3 days before inoculation. Early treatment of established retinitis with HPMPC markedly delayed the progression of the infection. However, with ganciclovir there was delayed progression only in rabbits treated 3 days after viral inoculation. HPMPC had a remarkably potent and prolonged (⩽1 month) antiviral effect in this retinitis model and may prove more useful than ganciclovirin local treatment of CMV retinitis.