Potent anti-murine cytomegalovirus activity and reduced nephrotoxicity of ganciclovir cyclic phosphonate.

Abstract

Ganciclovir cyclic phosphonate (SR3775) is a derivative of the R enantiomer (SR3773) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine), both of which are potent inhibitors of human ctyomegalovirus and murine cytomegalovirus (MCMV). Against wild-type and four drug-resistant strains of MCMV, SR3773 was 2.3- to 3-fold more potent than SR3775. SR3775 was about half as active as SR3773 against MCMV infections in severe combined immunodeficient mice. However, whereas 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. SR3775 has a therapeutic index at least 12 times higher than SR3773 in mice, making it a candidate for the treatment of human cytomegalovirus disease.

• Authors: D F Smee, E J Reist
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 40 Issue 8 Pg. 1964-6 (Aug 1996) ISSN: 0066-4804 [Print] United States
• PMID: 8843317 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antiviral Agents
• Cyclic P-Oxides
• Organophosphonates
• ganciclovir cyclic phosphonate
• 9-(1-hydroxy-4-phosphinyl-2-butoxymethyl)guanine
• Ganciclovir

Topics

• Animals
• Antiviral Agents (pharmacology, therapeutic use, toxicity)
• Cell Line
• Cyclic P-Oxides (pharmacology, therapeutic use, toxicity)
• Female
• Ganciclovir (analogs & derivatives, pharmacology, therapeutic use, toxicity)
• Herpesviridae Infections (drug therapy, virology)
• Kidney Tubules, Proximal (drug effects)
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Microbial Sensitivity Tests
• Muromegalovirus (drug effects)
• Organophosphonates
• Stereoisomerism
• Viral Plaque Assay