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  • Title: Lack of retinal toxicity of the anticytomegalovirus drug (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine.
    Author: Dolnak DR, Munguia D, Wiley CA, De Clercq E, Bergeron-Lynn GL, Boscher C, Connor JD, Sherwood C, Capparelli E, Armani R.
    Journal: Invest Ophthalmol Vis Sci; 1992 Apr; 33(5):1557-63. PubMed ID: 1559752.
    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.
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