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. 1985 Feb;27(2):167–171. doi: 10.1128/aac.27.2.167

Oral acyclovir therapy of genital herpes simplex virus type 2 infections in guinea pigs.

M N Ellis, D W Barry
PMCID: PMC176231  PMID: 2984984

Abstract

Oral acyclovir was evaluated for its effectiveness in treating guinea pigs with primary herpes simplex virus type 2 infections. Guinea pigs inoculated intravaginally with acyclovir-susceptible strains (for which 50% inhibitory concentrations of acyclovir in cell culture were found to be in the range of 0.15 to 1.2 micrograms/ml) and treated with 5.0 mg of acyclovir per ml in the drinking water beginning 48 h postinfection showed significant reductions in lesion severity. This dosage produced serum acyclovir levels of 1.3 micrograms/ml. Lower concentrations of oral acyclovir (less than or equal to 2.5 mg/ml in the drinking water), which produced serum acyclovir levels of less than 1.0 microgram/ml, were less consistently effective against these same virus strains. When an acyclovir-resistant isolate (for which the 50% inhibitory concentration of acyclovir in cell culture was found to be 8.5 micrograms/ml) was used to initiate infection, treatment with 5 or 10 mg/ml (yielding serum levels of 1.3 and 3.5 micrograms/ml) in the drinking water had only minimal clinical benefit. However, the degree of response was difficult to determine because of the attenuated disease produced by the acyclovir-resistant virus. In vitro virus sensitivity may be predictive of the serum drug levels that need to be obtained to produce a successful response to therapy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson C. A., August M. J., Hsiung G. D. Pathogenicity of wild-type and temperature-sensitive mutants of herpes simplex virus type 2 in guinea pigs. Infect Immun. 1980 Oct;30(1):159–169. doi: 10.1128/iai.30.1.159-169.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burns W. H., Saral R., Santos G. W., Laskin O. L., Lietman P. S., McLaren C., Barry D. W. Isolation and characterisation of resistant Herpes simplex virus after acyclovir therapy. Lancet. 1982 Feb 20;1(8269):421–423. doi: 10.1016/s0140-6736(82)91620-8. [DOI] [PubMed] [Google Scholar]
  3. Crumpacker C. S., Schnipper L. E., Marlowe S. I., Kowalsky P. N., Hershey B. J., Levin M. J. Resistance to antiviral drugs of herpes simplex virus isolated from a patient treated with acyclovir. N Engl J Med. 1982 Feb 11;306(6):343–346. doi: 10.1056/NEJM198202113060606. [DOI] [PubMed] [Google Scholar]
  4. Field H. J., Darby G. Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo. Antimicrob Agents Chemother. 1980 Feb;17(2):209–216. doi: 10.1128/aac.17.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Field H. J. Development of clinical resistance to acyclovir in herpes simplex virus-infected mice receiving oral therapy. Antimicrob Agents Chemother. 1982 May;21(5):744–752. doi: 10.1128/aac.21.5.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harmenberg J. Intracellular pools of thymidine reduce the antiviral action of acyclovir. Intervirology. 1983;20(1):48–51. doi: 10.1159/000149373. [DOI] [PubMed] [Google Scholar]
  7. Hirano A., Yumura K., Kurimura T., Katsumoto T., Moriyama H., Manabe R. Analysis of herpes simplex virus isolated from patients with recurrent herpes keratitis exhibiting "treatment-resistance" to 5-iodo-2'-deoxyuridine. Acta Virol. 1979 May;23(3):226–230. [PubMed] [Google Scholar]
  8. Hsiung G. D., Mayo D. R., Lucia H. L., Landry M. L. Genital herpes: pathogenesis and chemotherapy in the guinea pig model. Rev Infect Dis. 1984 Jan-Feb;6(1):33–50. doi: 10.1093/clinids/6.1.33. [DOI] [PubMed] [Google Scholar]
  9. Kern E. R. Acyclovir treatment of experimental genital herpes simplex virus infections. Am J Med. 1982 Jul 20;73(1A):100–108. doi: 10.1016/0002-9343(82)90073-0. [DOI] [PubMed] [Google Scholar]
  10. Landry M. L., Lucia H. L., Hsiung G. D., Pronovost A. D., Dann P. R., August M. J., Mayo D. R. Effect of acyclovir on genital infection with herpes simplex virus types 1 and 2 in the guinea pig. Am J Med. 1982 Jul 20;73(1A):143–150. doi: 10.1016/0002-9343(82)90080-8. [DOI] [PubMed] [Google Scholar]
  11. Lukás B., Wiesendanger W., Schmidt-Ruppin K. H. Genital herpes in guinea-pigs. An experimental model with Herpesvirus hominis. Arch Gesamte Virusforsch. 1974;44(2):153–155. doi: 10.1007/BF01250226. [DOI] [PubMed] [Google Scholar]
  12. McLaren C., Ellis M. N., Hunter G. A. A colorimetric assay for the measurement of the sensitivity of herpes simplex viruses to antiviral agents. Antiviral Res. 1983 Nov;3(4):223–234. doi: 10.1016/0166-3542(83)90001-3. [DOI] [PubMed] [Google Scholar]
  13. Myerson D., Hsiung G. D. Prophylactic and therapeutic treatment with acyclovir of genital herpes in the guinea pig. Proc Soc Exp Biol Med. 1983 Nov;174(2):147–152. doi: 10.3181/00379727-174-41717. [DOI] [PubMed] [Google Scholar]
  14. Pronovost A. D., Lucia H. L., Dann P. R., Hsiung G. D. Effect of acyclovir on genital herpes in guinea pigs. J Infect Dis. 1982 Jun;145(6):904–908. doi: 10.1093/infdis/145.6.904. [DOI] [PubMed] [Google Scholar]
  15. Quinn R. P., de Miranda P., Gerald L., Good S. S. A sensitive radioimmunoassay for the antiviral agent BW248U [9-(2-hydroxyethoxymethyl)guanine]. Anal Biochem. 1979 Oct 1;98(2):319–328. doi: 10.1016/0003-2697(79)90148-9. [DOI] [PubMed] [Google Scholar]
  16. Sibrack C. D., Gutman L. T., Wilfert C. M., McLaren C., St Clair M. H., Keller P. M., Barry D. W. Pathogenicity of acyclovir-resistant herpes simplex virus type 1 from an immunodeficient child. J Infect Dis. 1982 Nov;146(5):673–682. doi: 10.1093/infdis/146.5.673. [DOI] [PubMed] [Google Scholar]
  17. Van Dyke R. B., Connor J. D., Wyborny C., Hintz M., Keeney R. E. Pharmacokinetics of orally administered acyclovir in patients with herpes progenitalis. Am J Med. 1982 Jul 20;73(1A):172–175. doi: 10.1016/0002-9343(82)90085-7. [DOI] [PubMed] [Google Scholar]
  18. Wade J. C., McLaren C., Meyers J. D. Frequency and significance of acyclovir-resistant herpes simplex virus isolated from marrow transplant patients receiving multiple courses of treatment with acyclovir. J Infect Dis. 1983 Dec;148(6):1077–1082. doi: 10.1093/infdis/148.6.1077. [DOI] [PubMed] [Google Scholar]
  19. Weinstein L., Dalton A. C. Host determinants of response to antimicrobial agents. N Engl J Med. 1968 Aug 29;279(9):467–contd. doi: 10.1056/NEJM196808292790905. [DOI] [PubMed] [Google Scholar]

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