Antiviral Res. 1994 Feb;23(2):93-105.
Efficacy of A-73209, a potent orally active agent against VZV and HSV infections.

Alder J, Mitten M, Norbeck D, Marsh K, Kern ER, Clement J.

Abbott Laboratories, Department 47T, Abbott Park, IL 60064-3500.

A-73209 is a novel oxetanocin derivative with potent in vitro and in vivo activity against VZV, HSV-1, and HSV-2. A-73209 was two logs more potent than acyclovir against five thymidine kinase positive (TK+) strains of VZV in vitro (mean EC50 0.01 vs. 1.22 micrograms/ml). The activity of A-73209 was one log more potent than acyclovir against TK+ HSV-1 strains in vitro (EC50 = 0.03 vs. 0.32 micrograms/ml). A-73209 yielded a mean EC50 of 2.2 micrograms/ml compared to a mean EC50 of 0.37 micrograms/ml for acyclovir against a panel of TK+ HSV-2 strains in vitro. The in vitro activity of A-73209 against thymidine kinase negative or deficient strains of VZV, HSV-1 and HSV-2 was much lower than for the corresponding TK+ strains. A-73209 produced efficacy superior to acyclovir against lethal systemic or intracerebral HSV-1 infections in mice. The greater efficacy of A-73209 relative to acyclovir was especially apparent with oral dosing. Against HSV-2 infections in mice, the efficacy of A-73209 ranged from equal to 1.7 times less active relative to acyclovir with oral dosing. A-73209 was orally bioavailable in mice, with maximal serum concentrations well in excess of in vitro inhibitory concentrations. A-73209 appears to be a potent and selective agent against varicella-zoster virus and herpes simplex virus infections.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8147583&dopt=Abstract acyclovir Zovirax

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Herpes simplex virus (HSV) isolates were characterized from 8 AIDS patients in whom acyclovir and foscarnet therapy sequentially failed. The 6 postacyclovir (prefoscarnet) HSV isolates were resistant to acyclovir and susceptible to foscarnet. Of the 9 postfoscarnet isolates, 8 were foscarnet-resistant and acyclovir-susceptible, 1 was resistant to both drugs. Acyclovir- or foscarnet-resistant isolates retained susceptibility to cidofovir. The acyclovir-resistant isolates contained single-base substitutions or frameshift mutations in G or C homopolymer nucleotide repeats of the thymidine kinase gene. In contrast, the foscarnet-resistant strains contained single-base substitutions in conserved (II, III, or VI) or, more rarely, nonconserved (between I and VII) regions of the DNA polymerase (pol) gene. The single isolate exhibiting resistance to acyclovir and foscarnet contained mutations in both genes. In this study of clinical HSV isolates, DNA pol mutations conferring foscarnet resistance were not associated with decreased acyclovir or cidofovir susceptibility.

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Retina. 1997;17(1):57-64.
Evaluation of a novel lipid prodrug for intraocular drug delivery: effect of acyclovir diphosphate dimyristoylglycerol in a rabbit model with herpes simplex virus-1 retinitis.

Taskintuna I, Banker AS, Flores-Aguilar M, Bergeron-Lynn G, Aldern KA, Hostetler KY, Freeman WR.

Department of Ophthalmology, University of California, San Diego, USA.

BACKGROUND: Acyclovir diphosphate dimyristoylglycerol is a lipid prodrug of acyclovir that forms liposomes and provides substantial activity against herpes simplex virus, acyclovir-resistant strains of herpes simplex virus, and human cytomegalovirus. We therefore tested this promising new drug in a rabbit model of herpes simplex retinitis. METHODS: A total of 22 pigmented rabbits were pretreated with either acyclovir diphosphate dimyristoylglycerol, ganciclovir, acyclovir, or buffer. Retinae then were inoculated with herpes simplex virus-1 or buffer 1 week after the injection of drug. In another experiment we compared the effects of acyclovir diphosphate dimyristoylglycerol and acyclovir diphosphate dioleoylglycerol on the optical clarity of vitreous. RESULTS: Animals injected intravitreally with acyclovir diphosphate dimyristoylglycerol showed retinitis that was less severe than that in animals injected with ganciclovir, acyclovir, and buffer; differences in grading scores of the retinitis between animals injected with acyclovir diphosphate dimyristoylglycerol and those injected with buffer were statistically significant (P = 0.0015). Vitreous and optical media became clear 4 days after acyclovir diphosphate dioleoylglycerol injection compared with 10 days after with acyclovir diphosphate dimyristoylglycerol injections. CONCLUSION: Acyclovir diphosphate dimyristoylglycerol had prolonged antiviral activity against herpes simplex virus-1 retinitis in a rabbit model. This drug delivery system, modified to improve optical clarity, may allow long-acting intravitreal treatment of cytomegalovirus retinitis and other retinal diseases.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9051844&dopt=Abstract acyclovir Zovirax




Acta Med Austriaca. 1998;25(2):57-60.
Herpes simplex infection as possible etiology for febrile neutropenia and mucositis in patients treated for hematological malignancies.

Kubesova H, Penka M, Kral Z, Adam Z, Vasova I, Tomiska M, Vorlicek J.

Department of Internal Medicine, Masaryk University Hospital, Brno, Czech Republic.

Mucositis is a common complication following chemotherapy. Clinical findings similar to herpetic infection are observed in some patients. Acyclovir administered in addition to empirical, antibiotic treatment improves the course of mucositis, and can also bring down the temperature. The aim of our study was to define the etiological influence of herpetic infection on the course of febrile neutropenia in patients with mucositis. A total of 34 patients with febrile neutropenia were divided into 2 groups: 15 with typical herpetic eruption, and 19 with non-specific mucositis. Both groups received 5-10 mg/kg acyclovir every eight hours together with empiric antibiotic treatment. The effect of acyclovir was studied, and results compared in the two patient groups. Body temperatures decreased in both groups, clinical symptoms, however, disappeared more slowly in the group with non-specific mucositis. The beneficial effect of acyclovir treatment was particularly well expressed in seropositive patients. In this group of patients, herpetic infections may recur under further chemotherapy. Thus, it would be useful to administer acyclovir to them prophylactically during risk periods.

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J Med Virol. 1996 Nov;50(3):244-8.
Effect of acyclovir and prednisolone on the serological response in herpes zoster.

Bates CJ, Kudesia G, McKendrick MW.

Sheffield Public Health Laboratory, England.

The serological response of patients with acute herpes zoster was studied to determine whether a diagnosis could be made on a single serum sample, and whether this response was modified by treatment with antiviral and/or steroid therapy. The patients received one of four regimes of acyclovir and prednisolone, Varicella zoster virus (VZV) IgG, IgM, and IgA responses were measured by commercial and in-house enzyme immunoassays (EIA) using serum samples taken at days 0, 7, and 21 after entry into the study. Samples were also tested for IgM to Epstein-Barr virus (EBV) viral capsid antigen (VCA), and cytomegalovirus (CMV) IgM and for herpes simplex virus (HSV) antibodies by the complement fixation test (CFT). Analysis was carried out on data from 71 patients. VZV IgM was detected in 72%, VZV IgA in 78%, and either VZV IgM or IgA in 88% of patients tested, at some time during the 3-week study period. The optimal time to detect either class of antibody was approximately 1 week after the onset of the vesicular rash, when 85% of patients had one or both classes of acute phase antibody in their serum. There was no evidence of cross reaction with EBV, CMV, or HSV antibodies. Neither treatment with prednisolone nor the length of therapy with acyclovir affected significantly the VZV IgM or IgA responses. Therefore it is possible to make a serological diagnosis of herpes zoster on a single sample, optimally 1 week after the onset of the rash, in patients treated with acyclovir alone or with acyclovir and steroids.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8923289&dopt=Abstract acyclovir Zovirax