Abstract
The effects of famciclovir (FCV) and valaciclovir (VACV) were compared in a cutaneous infection model for herpes simplex virus type 2 (HSV-2). The compounds were administered orally from day 1 to day 5 postinfection. Both compounds reduced local inflammation and virus replication in the skin. FCV markedly reduced mortality and virus replication in the nervous system. On the cessation of therapy after 5 days, when the levels of infectious virus in the tissues were reduced to below the level of detection, there followed a rebound of virus replication in the ganglia and brain stems of mice that had been treated with VACV. The recurrence of infection in the brain stem occurred on three separate occasions. No such recurrences were observed following FCV treatment. When ganglia were explanted from survivors 6 weeks later, latent virus was shown to be reactivated in all 10 of 10 control, untreated mice. The number of mice whose ganglia yielded virus was reduced to 60% in mice that had been treated with VACV, whereas no mice that had been treated with FCV had evidence of latent infection by this test.
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Selected References
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- Blyth W. A., Harbour D. A., Hill T. J. Effect of acyclovir on recurrence of herpes simplex skin lesions in mice. J Gen Virol. 1980 Jun;48(Pt 2):417–419. doi: 10.1099/0022-1317-48-2-417. [DOI] [PubMed] [Google Scholar]
- Earnshaw D. L., Bacon T. H., Darlison S. J., Edmonds K., Perkins R. M., Vere Hodge R. A. Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. Antimicrob Agents Chemother. 1992 Dec;36(12):2747–2757. doi: 10.1128/aac.36.12.2747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Field H. J., Bell S. E., Elion G. B., Nash A. A., Wildy P. Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice. Antimicrob Agents Chemother. 1979 Apr;15(4):554–561. doi: 10.1128/aac.15.4.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Field H. J., De Clercq E. Effects of oral treatment with acyclovir and bromovinyldeoxyuridine on the establishment of maintenance of latent herpes simplex virus infection in mice. J Gen Virol. 1981 Oct;56(Pt 2):259–265. doi: 10.1099/0022-1317-56-2-259. [DOI] [PubMed] [Google Scholar]
- Field H. J., Tewari D., Sutton D., Thackray A. M. Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model. Antimicrob Agents Chemother. 1995 May;39(5):1114–1119. doi: 10.1128/aac.39.5.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Field H. J., Wildy P. The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (Lond) 1978 Oct;81(2):267–277. doi: 10.1017/s0022172400025109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harnden M. R., Jarvest R. L., Boyd M. R., Sutton D., Vere Hodge R. A. Prodrugs of the selective antiherpesvirus agent 9-[4-hydroxy-3-(hydroxymethyl)but-1-yl]guanine (BRL 39123) with improved gastrointestinal absorption properties. J Med Chem. 1989 Aug;32(8):1738–1743. doi: 10.1021/jm00128a012. [DOI] [PubMed] [Google Scholar]
- Hodge R. A., Perkins R. M. Mode of action of 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine (BRL 39123) against herpes simplex virus in MRC-5 cells. Antimicrob Agents Chemother. 1989 Feb;33(2):223–229. doi: 10.1128/aac.33.2.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein R. J., Friedman-Kien A. E., DeStefano E. Effect of discontinuous acyclovir treatment on in vitro reactivation of herpes simplex virus from latently infected trigeminal ganglia. Antimicrob Agents Chemother. 1983 Jul;24(1):129–131. doi: 10.1128/aac.24.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein R. J., Friedman-Kien A. E., DeStefano E. Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Antimicrob Agents Chemother. 1979 May;15(5):723–729. doi: 10.1128/aac.15.5.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein R. J., Friedman-Kien A. E. Effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the acute local phase of herpes simplex virus-induced skin infections in mice and the establishment of latency. Antimicrob Agents Chemother. 1985 May;27(5):763–768. doi: 10.1128/aac.27.5.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein R. J., Friedman-Kien A. E., Kaley L., Brady E. Effects of topical applications of phosphonoacetate on colonization of mouse trigeminal ganglia with herpes simplex virus type 1. Antimicrob Agents Chemother. 1984 Jul;26(1):65–68. doi: 10.1128/aac.26.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nash A. A., Field H. J., Quartey-Papafio R. Cell-mediated immunity in herpes simplex virus-infected mice: induction, characterization and antiviral effects of delayed type hypersensitivity. J Gen Virol. 1980 Jun;48(Pt 2):351–357. doi: 10.1099/0022-1317-48-2-351. [DOI] [PubMed] [Google Scholar]
- Sutton D., Boyd M. R. Comparative activity of penciclovir and acyclovir in mice infected intraperitoneally with herpes simplex virus type 1 SC16. Antimicrob Agents Chemother. 1993 Apr;37(4):642–645. doi: 10.1128/aac.37.4.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thackray A. M., Field H. J. Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency. J Infect Dis. 1996 Feb;173(2):291–299. doi: 10.1093/infdis/173.2.291. [DOI] [PubMed] [Google Scholar]
- Thouless M. E. Serological properties of thymidine kinase produced in cells infected with type 1 or type 2 herpes virus. J Gen Virol. 1972 Dec;17(3):307–315. doi: 10.1099/0022-1317-17-3-307. [DOI] [PubMed] [Google Scholar]
- Vere Hodge R. A., Sutton D., Boyd M. R., Harnden M. R., Jarvest R. L. Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir]. Antimicrob Agents Chemother. 1989 Oct;33(10):1765–1773. doi: 10.1128/aac.33.10.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vere Hodge R. A., Sutton D., Boyd M. R., Harnden M. R., Jarvest R. L. Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir]. Antimicrob Agents Chemother. 1989 Oct;33(10):1765–1773. doi: 10.1128/aac.33.10.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weller S., Blum M. R., Doucette M., Burnette T., Cederberg D. M., de Miranda P., Smiley M. L. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993 Dec;54(6):595–605. doi: 10.1038/clpt.1993.196. [DOI] [PubMed] [Google Scholar]