EFFECT OF 9-(4-HYDROXYBUTYL)-N-2-PHENYLGUANINE (HBPG), A THYMIDINE KINASE INHIBITOR, ON CLINICAL RECURRENCES OF OCULAR HERPETIC-KERATITIS IN SQUIRREL-MONKEYS

9-(4-Hydroxybutyl)-N-2-phenylguanine (HPG) is a new viral thymidine ki nase inhibitor that we tested for the ability to prevent recurrences o f herpetic keratitis. Eighteen squirrel monkeys (Saimiri scuireus) wer e infected in both corneas with the Rodanus strain of herpes simplex v irus 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 HB PG, 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, rec urrences were induced by reducing the temperature of the room in the l ate afternoon so that a low of 18 degrees C was achieved during the ni ght. After the morning treatment, room temperature was raised to the n ormal ambient temperature (24-27 degrees C), and treatment was discont inued. Treatment was reinstituted on day 27, the room temperature was lowered again on day 28, and treatment was again discontinued as befor e. Third and fourth cycles of treatment and cold stress were begun on days 34 and 69. Ocular examinations were continued until day 73, at wh ich point the code was broken. We found that the HBPG treatment signif icantly reduced the number of corneas with recurrences during the trea tment periods, compared with recurrences in untreated, cold-stressed a nimals (P = 0.01).