Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.
(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency antiherpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of experimental retinitis caused by preretinal herpes simplex virus (HSV-1) injection in rabbits. HPMPC (100 micrograms/0.1 mL) was intravitreally injected 10, 15, 21, 30, or 46 days before, concurrently, or 3, 5, or 7 days after viral inoculation. Ganciclovir (200 micrograms/0.1 mL) was intravitreally injected 3, 7, or 10 days before HSV-1 inoculation, concurrent with viral inoculation, or 3, 5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected from retinitis for 15-21 days. Ganciclovir did not protect completely even if administered 3 days before inoculation. Early treatment of established retinitis with HPMPC markedly delayed the progression of the infection. However, with ganciclovir there was delayed progression only in rabbits treated 3 days after viral inoculation. HPMPC had a remarkably potent and prolonged (< or = 1 month) antiviral effect in this retinitis model and may prove more useful than ganciclovir in local treatment of CMV retinitis.
Flores-Aguilar
M
M
Department of Ophthalmology, University of California, School of Medicine, San Diego, La Jolla.
Huang
J S
JS
Wiley
C A
CA
De Clercq
E
E
Vuong
C
C
Bergeron-Lynn
G
G
Chandler
B
B
Munguia
D
D
Freeman
W R
WR
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use* / Q000633:toxicity; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D004359:Drug Therapy, Combination; D015774:Ganciclovir / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use* / Q000633:toxicity; D011817:Rabbits; D012173:Retinitis / Q000188:drug therapy* / Q000382:microbiology; D013997:Time Factors
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir