April 1992
Volume 33, Issue 5
Free
Articles  |   April 1992
Lack of retinal toxicity of the anticytomegalovirus drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine.
Author Affiliations
  • D R Dolnak
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • D Munguia
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • C A Wiley
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • E De Clercq
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • G L Bergeron-Lynn
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • C Boscher
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • J D Connor
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • C Sherwood
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • E Capparelli
    Department of Ophthalmology, University of California, San Diego 92093-0946.
  • R Armani
    Department of Ophthalmology, University of California, San Diego 92093-0946.
Investigative Ophthalmology & Visual Science April 1992, Vol.33, 1557-1563. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      D R Dolnak, D Munguia, C A Wiley, E De Clercq, G L Bergeron-Lynn, C Boscher, J D Connor, C Sherwood, E Capparelli, R Armani; Lack of retinal toxicity of the anticytomegalovirus drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine.. Invest. Ophthalmol. Vis. Sci. 1992;33(5):1557-1563.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

The drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC) is an antiherpesvirus group compound with a higher potency and longer duration of action against human cytomegalovirus (CMV) than ganciclovir or foscarnet. Twenty eyes of ten New Zealand white rabbits received 0.1-ml injections of either normal saline or HPMPC at doses of 10, 50, 100, 300, or 1000 micrograms. The animals were killed on days 14 and 28. Toxicity was assessed by indirect ophthalmoscopy, electroretinography (ERG), and light and electron microscopy. Both a- and b-wave ERG findings and indirect ophthalmoscopic appearance of retinas in all groups were normal. Light and electron microscopy of perfusion-fixed retinal tissue revealed no morphologic changes at doses of 100 micrograms or lower. The pharmacokinetics of eight rabbits injected intravitreally with 100 micrograms of HPMPC showed a 24.4-hr half-life for the drug. These results indicate that HPMPC is not toxic to the rabbit retina at 500-1000-fold the dose that is effective in suppressing CMV infections. Doses of 100 micrograms also were injected into the vitreous of monkey eyes. Intravitreal injections of HPMPC may be efficacious in inhibiting CMV retinitis for longer dosing intervals than can be used with other anti-CMV compounds.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×