Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine (BRL 39123) in animals.

Abstract

The antiviral activity of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) was assessed in several animal models of herpes simplex virus (HSV) infection. BRL 39123 was as active as acyclovir (ACV) when applied topically to guinea pigs with a cutaneous HSV type 1 (HSV-1) infection and was also active topically in an HSV-2 genital infection. Before systemic administration to infected animals, BRL 39123 and ACV were administered orally and subcutaneously to mice, and the blood was assayed for each compound by high-pressure liquid chromatography. When given systemically to mice infected cutaneously with HSV-1, BRL 39123 was as active as ACV. In mice infected intranasally with HSV-1 or HSV-2, single daily subcutaneous doses of BRL 39123 were more effective than equivalent treatment with ACV, reflecting the more persistent activity seen in cell culture and a more stable triphosphate within the infected cell. When the compounds were supplied in drinking water for this infection, BRL 39123 and ACV had similar potencies against HSV-1, although ACV was more active against an HSV-2 infection than BRL 39123 was. In mice infected intraperitoneally with HSV-1, BRL 39123 was 10-fold more potent than ACV and a single dose of BRL 39123 reduced virus replication within the peritoneal cavity more effectively than 3 doses of ACV given 1, 5, and 20 h after infection. Although BRL 39123 failed to eradicate the virus from mice latently infected with HSV-1, treatment initiated 5 h after infection of the ear pinna reduced the numbers of mice that developed latent infections.

• Authors: M R Boyd, T H Bacon, D Sutton
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 32 Issue 3 Pg. 358-63 (Mar 1988) ISSN: 0066-4804 [Print] United States
• PMID: 3364954 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• penciclovir
• Guanine
• Acyclovir

Topics

• Acyclovir (analogs & derivatives, therapeutic use)
• Animals
• Antiviral Agents (therapeutic use)
• Biological Availability
• Chromatography, High Pressure Liquid
• Female
• Guanine
• Guinea Pigs
• Herpes Simplex (drug therapy, microbiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Mice, Nude
• Peritoneal Diseases (drug therapy, microbiology)
• Skin Diseases, Infectious (drug therapy, microbiology)