Liposome-encapsulated (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for long-acting therapy of viral retinitis.
The effect of liposome-encapsulated (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC; cidofovir) was evaluated as prophylaxis in a rabbit model of experimentally induced retinitis caused by preretinal inoculation of herpes simplex virus type 1 (HSV-1). Cidofovir (100 micrograms) in liposomes (0.1 mL) was injected intravitreally 10-120 days before retinal inoculation with HSV-1. Twenty-two of 26 eyes pretreated with liposome-encapsulated cidofovir 10-60 days before HSV-1 inoculation were protected from experimentally induced retinitis, and 2 of 5 eyes pretreated 120 days before inoculation were protected. Intravitreal levels of cidofovir were low (0.7 microgram/mL) but detectable 120 days after injection. One 100-micrograms intravitreal injection of liposome-encapsulated cidofovir appears to have a remarkably potent and prolonged (up to 4 months) antiviral effect in this experimental model of HSV-1 retinitis. Since HPMPC is even more potent against cytomegalovirus than HSV-1, liposome-encapsulated cidofovir may prove to be effective local therapy for AIDS patients with cytomegalovirus retinitis.
Department of Ophthalmology, University of California, San Diego, La Jolla 92093, USA.
B D
BD
Kuppermann
K K
KK
Assil
C
C
Vuong
G
G
Besen
C A
CA
Wiley
E
E
De Clercq
G
G
Bergeron-Lynn
J D
JD
Connor
M
M
Pursley
D
D
Munguia
W R
WR
Freeman
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004337:Drug Carriers; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology; D007267:Injections; D008081:Liposomes; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D011817:Rabbits; D012160:Retina / Q000473:pathology / Q000821:virology; D012173:Retinitis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014822:Vitreous Body
D000998:Antiviral Agents; D004337:Drug Carriers; D008081:Liposomes; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir