Document 0462
 DOCN  M9460462
 TI    Toxicologic and pharmacokinetic analysis of intravitreal injections of
       foscarnet, either alone or in combination with ganciclovir.
 DT    9404
 AU    Berthe P; Baudouin C; Garraffo R; Hofmann P; Taburet AM; Lapalus P;
       Laboratory of Pharmacology, School of Medicine, Nice, France.
 SO    Invest Ophthalmol Vis Sci. 1994 Mar;35(3):1038-45. Unique Identifier :
       AIDSLINE MED/94171479
 AB    PURPOSE. The retinal toxicity of single and repeated intravitreal
       injections of foscarnet was investigated. In addition, the effects of a
       combination of foscarnet and ganciclovir were studied, and a
       pharmacokinetic study to determine the ocular pharmacokinetics of
       foscarnet after intravitreal injection was carried out. METHODS. Forty
       rabbits (both albino and pigmented) were used in this study. The
       electroretinographic (ERG) a-waves and b-waves and oscillatory
       potentials (OP) were used as as indicators of retinal toxicity.
       Potential toxicity was also assessed by ophthalmoscopy and histologic
       studies (light and electron microscopy). RESULTS. The a-wave and b-wave
       were not deteriorated with 2.4 mg foscarnet after single or repeated
       injections. The OP remained unchanged. There was no ERG change after
       intravitreal injection of a combination of both drugs. No evidence of
       retinal toxicity was observed by indirect ophthalmoscopy in any case.
       Light and electron microscopy on semithin sections of retina failed to
       demonstrate any adverse effects, and showed normal organization and
       cytoarchitecture of all the layers of the retina without evidence of
       cytopathology. The ocular pharmacokinetics of foscarnet determined by
       noncompartmental analysis showed a 34-hour terminal elimination
       half-life and an apparent volume of distribution of 1.9 ml. CONCLUSIONS.
       Based on these results, high doses of foscarnet were not judged toxic to
       the rabbit retina, with single or repeated injections. Moreover,
       concomitant injection of the two drugs did not induce any retinal
       toxicity. These findings suggest that when systemic treatment is to be
       stopped in patients with AIDS for toxic side effects, either ganciclovir
       or foscarnet may be used intravitreally as an alternative. Because a
       combination of the two drugs has been shown to be synergistic, both
       ganciclovir and foscarnet might be simultaneously injected into the
       vitreous cavity to block progression of cytomegalovirus retinitis.
 DE    Animal  Aqueous Humor/METABOLISM  Drug Combinations  Electrophysiology
       Electroretinography  Foscarnet/*PHARMACOKINETICS/*TOXICITY
       Ganciclovir/*PHARMACOKINETICS/*TOXICITY  Half-Life  Injections
       Ophthalmoscopy  Rabbits  Retina/*DRUG
       EFFECTS/*METABOLISM/PHYSIOPATHOLOGY  Support, Non-U.S. Gov't  Vitreous
       Body  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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