Cyclic HPMPC is safe and effective against systemic guinea pig cytomegalovirus infection in immune compromised animals

Nigel Bourne, F. J. Bravo, D. I. Bernstein

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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]cytosine 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. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)103-109
Number of pages7
JournalAntiviral Research
Volume47
Issue number2
DOIs
StatePublished - Aug 2000
Externally publishedYes

Fingerprint

Roseolovirus
Cytomegalovirus Infections
Guinea Pigs
Therapeutics
Cytomegalovirus Retinitis
Safety
Herpesviridae Infections
Liver
Virus Diseases
Virus Replication
Salivary Glands
Cyclophosphamide
cyclic-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine
Acquired Immunodeficiency Syndrome
Spleen
Kidney
Lung
Mortality
cidofovir

Keywords

  • Antiviral
  • CHPMPC
  • Cytomegalovirus
  • Guinea pig
  • Immune compromised

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Cyclic HPMPC is safe and effective against systemic guinea pig cytomegalovirus infection in immune compromised animals. / Bourne, Nigel; Bravo, F. J.; Bernstein, D. I.

In: Antiviral Research, Vol. 47, No. 2, 08.2000, p. 103-109.

Research output: Contribution to journalArticle

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