Cyclic HPMPC is safe and effective against systemic guinea pig cytomegalovirus infection in immune compromised animals.
Cidofovir (HPMPC) is licensed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS but its use is limited by nephrotoxicity. We evaluated the safety and efficacy of 1-[((s)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosi ne dihydrate (CHPMPC) the cyclic congener of cidofovir. Treatment was well tolerated both in normal guinea pigs and in animals immune compromised with cyclophosphamide. Further, blood chemistry analysis showed no adverse effects of CHPMPC treatment on kidney or liver function. In efficacy studies in immune compromised guinea pigs challenged with a virulent salivary gland passaged guinea pig CMV, CHPMPC treatment significantly reduced mortality resulting from disseminated virus infection. Quantitative culture showed that treatment also significantly reduced virus replication in the liver and spleen, but not the lungs of infected animals. The efficacy of CHPMPC combined with its improved safety profile appear to make it an attractive alternative to cidofovir for the treatment of herpesvirus infections. Further evaluation is warranted.
Bourne
N
N
Children's Hospital Medical Center, Division of Infectious Diseases, 3333 Burnet Avenue, Cincinnati, OH, 45229-3039, USA. bourn@chmcc.org
Bravo
F J
FJ
Bernstein
D I
DI
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000494:pharmacology; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006168:Guinea Pigs; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007677:Kidney Function Tests; D008099:Liver / Q000821:virology; D008111:Liver Function Tests; D008168:Lung / Q000821:virology; D008297:Male; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D013154:Spleen / Q000821:virology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009943:Organophosphorus Compounds; C072572:cyclic-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine; D003596:Cytosine; D003520:Cyclophosphamide