Long-term therapy for herpes retinitis in an animal model with high-concentrated liposome-encapsulated HPMPC.
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.
Besen
G
G
Department of Ophthalmology, University of California-San Diego, La Jolla, USA.
Flores-Aguilar
M
M
Assil
K K
KK
Kupperman
B D
BD
Gangan
P
P
Pursley
M
M
Munguia
D
D
Vuong
C
C
De Clercq
E
E
Bergeron-Lynn
G
G
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
D000998:Antiviral Agents; D008081:Liposomes; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir