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Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients

Eperimental toxicity and pharmacokinetics, and clinical trial

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Abstract

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 μg/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.

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Abbreviations

AIDS:

acquired immunodeficiency syndrome

AZT:

zidovudine

CMV:

cytomegalovirus

GCV:

ganciclovir

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Authors and Affiliations

  1. Experimental Ophthalmology Unit, Department of Surgery, School of Medicine and Dentistry, University of Valencia, Spain

    Manuel Díaz-Llopis (Ass. Prof., Director Experimental Toxicology and Neurotoxicology Unit)

  2. Department of Ophthalmology, University Hospital ‘La Fe’, Valencia, Spain

    Manuel Díaz-Llopis (Ass. Prof., Director Experimental Toxicology and Neurotoxicology Unit), Enrique España, Manuel Cervera & Amparo Navea

  3. Colloids Research Unit, Department of Physico-Chemistry, School of Pharmacy, University of Valencia, Valencia

    M. José Martos, A. Ofelia Vila & Francisco J. Molina

  4. Experimental Toxicology and Neurotoxicology Unit, Department of Physiology, School of Medicine and Dentistry, University of Valencia, Valencia, Spain

    Francisco J. Romero

Authors
  1. Manuel Díaz-Llopis
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  2. M. José Martos
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  3. Enrique España
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  4. Manuel Cervera
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  5. A. Ofelia Vila
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  6. Amparo Navea
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  7. Francisco J. Molina
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  8. Francisco J. Romero
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Díaz-Llopis, M., Martos, M.J., España, E. et al. Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients. Doc Ophthalmol 82, 297–305 (1992). https://doi.org/10.1007/BF00161017

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