Effect of 9-(4-hydroxybutyl)-N2-phenylguanine (HBPG), a thymidine kinase inhibitor, on clinical recurrences of ocular herpetic keratitis in squirrel monkeys.
9-(4-Hydroxybutyl)-N2-phenylguanine (HBPG) is a new viral thymidine kinase inhibitor that we tested for the ability to prevent recurrences of herpetic keratitis. Eighteen squirrel monkeys (Saimiri scuireus) were infected in both corneas with the Rodanus strain of herpes simplex virus type 1 (HSV-1). All corneas showed typical dendritic keratitis 3 days after infection, followed by spontaneous healing. On day 21, the monkeys were randomized into two coded groups and ocular examinations were begun. One group received intraperitoneal (i.p.) injections of HBPG, 150 mg/kg, in a corn oil suspension every 8 h, and the other group received i.p. injections of the corn oil vehicle only. On day 22, recurrences were induced by reducing the temperature of the room in the late afternoon so that a low of 18 degrees C was achieved during the night. After the morning treatment, room temperature was raised to the normal ambient temperature (24-27 degrees C), and treatment was discontinued. Treatment was reinstituted on day 27, the room temperature was lowered again on day 28, and treatment was again discontinued as before. Third and fourth cycles of treatment and cold stress were begun on days 34 and 69. Ocular examinations were continued until day 73, at which point the code was broken. We found that the HBPG treatment significantly reduced the number of corneas with recurrences during the treatment periods, compared with recurrences in untreated, cold-stressed animals (P = 0.01).
Kaufman
H E
HE
Lions Eye Research Laboratories, LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans 70112, USA.
Varnell
E D
ED
Wright
G E
GE
Xu
H
H
Gebhardt
B M
BM
Thompson
H W
HW
D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D003315:Cornea / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D018259:Herpesvirus 1, Human; D006801:Humans; D007635:Keratitis, Dendritic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D012008:Recurrence; D012453:Saimiri; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*
C091724:9-(4-hydroxybutyl)-N(2)-phenylguanine; D000998:Antiviral Agents; D006147:Guanine; D013937:Thymidine Kinase