POTENT ANTIMURINE CYTOMEGALOVIRUS ACTIVITY AND REDUCED NEPHROTOXICITYOF GANCICLOVIR CYCLIC PHOSPHONATE

Ganciclovir cyclic phosphonate (SR3775) is a derivative of the R enant iomer (SR3773) of ganciclovir phosphonate ydroxymethyl-3-phosphono)pro pyloxymethyl]guanine), both of which are potent inhibitors of human cy tomegalovirus and murine cytomegalovirus (MCMV). Against wild-type and four drug-resistant strains of MCMV, SR3773 was 2.3- to 3-fold more p otent than SR3775. SR3775 was about half as active as SR3773 against M CMV infections in severe combined immunodeficient mice. However, where as SR3773 caused 20 to 30% destruction of renal tubules at 50 mg/kg of body weight per day (but exerted no toxicity at 25 mg/kg/day), SR3775 showed no deleterious renal effects at 600 mg/kg/day over 14 days; SR 3775 has a therapeutic index at least 12 times higher than that of SR3 773 in mice, making it a candidate for the treatment of human cytomega lovirus disease.