title: Long-term therapy for herpes retinitis in an animal model with high-concentrated liposome-encapsulated HPMPC.
abstract: OBJECTIVE
  To evaluate(s)-1-(3-hydroxy-2-phosphonyl methoxypropyl) cytosine (HPMPC), a potent antiherpes and anticytomegalovirus drug, as a long-term treatment of experimental retinitis in rabbits.
  
  
  METHODS
  The drug was first encapsulated into a liposome delivery system in three different concentrations and injected intravitreally. Sequentially, the highest concentration that was shown to be nontoxic to the retina was evaluated in a model of retinitis at 60, 90, 120, 170, and 240 days, after which herpes simplex virus type 1 was inoculated onto the retinal surface.
  
  
  RESULTS
  A dose of 1000 micrograms of HPMPC encapsulated in liposomes gives a protective effect for up to 8 months.
  
  
  CONCLUSIONS
  Reduced toxic effects and longer-term efficacy compared with free drug was observed. Given the 50 times higher activity of HPMPC against human cytomegalovirus than herpes simplex virus type 1, a single injection of 1000 micrograms of liposome-encapsulated HPMPC may have a very prolonged effect in the treatment of cytomegalovirus retinitis.
authors.affiliation: Department of Ophthalmology, University of California-San Diego, La Jolla, USA.
authors.forename: G
authors.initials: G
authors.lastname: Besen
authors.forename: M
authors.initials: M
authors.lastname: Flores-Aguilar
authors.forename: K K
authors.initials: KK
authors.lastname: Assil
authors.forename: B D
authors.initials: BD
authors.lastname: Kupperman
authors.forename: P
authors.initials: P
authors.lastname: Gangan
authors.forename: M
authors.initials: M
authors.lastname: Pursley
authors.forename: D
authors.initials: D
authors.lastname: Munguia
authors.forename: C
authors.initials: C
authors.lastname: Vuong
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: G
authors.initials: G
authors.lastname: Bergeron-Lynn
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D004195:Disease Models, Animal; D004596:Electroretinography; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000473:pathology; D005654:Fundus Oculi; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes; D008137:Longitudinal Studies; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011817:Rabbits; D012173:Retinitis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology
chemical_list: D000998:Antiviral Agents; D008081:Liposomes; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir