J Antimicrob Chemother. 1996 Feb;37(2):303-13.
Activity of penciclovir in antiviral assays against herpes simplex virus.

Bacon TH, Howard BA, Spender LC, Boyd MR.

SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, UK.

The effect of penciclovir and acyclovir on the replication of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains was determined in MRC-5 cells infected with 0.01 pfu/cell and exposed to the drugs for 72 h to allow multiple cycles of replication. Penciclovir was significantly more active than acyclovir against three strains of HSV-1 and three strains of HSV-2 at 1 mg/L (P = 0.009), 3 mg/L (P < 0.001) and 10 mg/L (P = 0.001). Further comparisons between the compounds were made in MRC-5 cells infected with HSV-1 strain SC16 using four different antiviral assays namely, the 24 h virus yield reduction assay, plaque reduction assay, viral antigen inhibition assay, and a viral DNA inhibition assay, to determine the relative merits of each. Penciclovir and acyclovir shared similar activities in the plaque reduction assay (with 50% effective concentrations, EC50, being 0.8 and 0.6 mg/L, respectively) and in the viral antigen inhibition assay (EC50s. 0.6 and 0.7 mg/L, respectively). The EC50 of penciclovir in the 24 h viral DNA inhibition assay was 0.01 mg/L compared with 0.06 mg/L of acyclovir. In the 24 h virus yield reduction assay in which MRC-5 cells were infected with 0.3 pfu/cell, penciclovir was more active than acyclovir with 99% effective concentrations of 0.6 mg/L and 1.1 mg/L, respectively. The activity of penciclovir in the 24 h virus yield reduction and antigen inhibition assays was inversely related to the multiplicity of infection, whereas this had considerably less effect on the inhibition of viral DNA synthesis. These results suggest that famciclovir, which is the oral form of penciclovir, will be at least as effective as acyclovir in treating infections caused by HSV-1 and HSV-2.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8707740&dopt=Abstract acyclovir Zovirax




Rapid Commun Mass Spectrom. 2002;16(19):1871-6.
Hydrophilic interaction liquid chromatography/electrospray mass spectrometry determination of acyclovir in pregnant rat plasma and tissues.

Brown SD, White CA, Bartlett MG.

College of Pharmacy, Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, Athens, GA 30602-2353, USA.

Reversed-phase chromatography is the most common means of separation for small drug molecules. However, polar drugs may suffer from poor retention and peak shape in reversed-phase high-performance liquid chromatography (RP-HPLC). Hydrophilic interaction liquid chromatography (HILIC) provides a viable alternative to RP-HPLC and is an excellent way to separate polar compounds. This paper describes a HILIC/ESI-MS/MS assay for the determination of acyclovir from rat plasma, amniotic fluid, placental tissue, and fetal tissue. The isocratic separation utilizes an underivatized silica column with an acetonitrile/formate buffer mobile phase (80:20). The method is validated over a range of 50 ng/mL to 50 micro g/mL with % error and % relative standard deviation of <15% over 3 days. All samples are prepared by acetonitrile protein precipitation, which yields high recovery (>84% for acyclovir). This assay can be applied to the pharmacokinetic study of the placental transfer of acyclovir. Copyright 2002 John Wiley & Sons, Ltd.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12271452&dopt=Abstract acyclovir Zovirax




J Clin Virol. 2002 Aug;25(2):165-70.
Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient.

Chibo D, Mijch A, Doherty R, Birch C.

Victorian Infectious Diseases Reference Laboratory, North Melbourne, Vic., Australia.

BACKGROUND: Mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus (HSV) may confer resistance to antiviral drugs, particularly in the context of immunosuppression induced by infection with the human immunodeficiency virus (HIV). OBJECTIVES: To characterise the HSV type 2 (HSV-2) TK and DNA pol genes in an immunocompromised patient with clinical resistance to both acyclovir and foscarnet. STUDY DESIGN: The TK and DNA pol genes of isolates obtained over a 2-year period from an AIDS patient with severe genital herpes infection were characterised both phenotypically and genotypically. RESULTS: HSV strains that were acyclovir resistant/foscarnet sensitive, acyclovir sensitive/foscarnet sensitive and acyclovir resistant/foscarnet resistant were isolated during this time. The TK gene of all the acyclovir resistant isolates contained a large 969 bp deletion which extended into a downstream untranslated region. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene. CONCLUSIONS: Clinical and virological suppression of the infection was not always associated with subsequent reactivation with wild-type virus. Mutations of the nature we describe have not previously been reported occurring simultaneously in HSV strains isolated from patients treated with acyclovir and foscarnet.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12367650&dopt=Abstract acyclovir Zovirax




Anticancer Res. 1996 Sep-Oct;16(5A):2623-8.
Evaluation of prodrugs ability to induce effective ablation of cells transduced with viral thymidine kinase gene.

Kuriyama S, Nakatani T, Masui K, Sakamoto T, Tominaga K, Yoshikawa M, Fukui H, Ikenaka K, Tsujii T.

Third Department of Internal Medicine, Nara Medical University, Japan.

Transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene into tumor cells followed by treatment with prodrugs is one of the most promising approaches for gene therapy in cancer. The choice of prodrugs is important in order to obtain maximum anticancer effects with minimum adverse reactions. We retrovirally transduced the HSV-tk gene into murine and rat hepatocellular carcinoma (HCC) cells, and investigated their sensitivity to ganciclovir and acyclovir. Retrovirally-mediated HSV-tk transduction did not affect cell proliferation, but led to both ganciclovir- and acyclovir-dependent cytotoxicity in the HCC cells. Ganciclovir exhibited much stronger cytotoxicity on HSV-tk transduced cells than acyclovir. Importantly, HSV-tk transduced cells were completely abrogated at a ganciclovir concentration which was lower than the minimum plasma level achieved in the clinical usage of ganciclovir. Furthermore, HSV-tk transduced cells induced stronger killing of neighboring untransduced cells in the presence of ganciclovir than acyclovir. Ganciclovir may be preferable to acyclovir in the HSV-tk transduction system.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8917361&dopt=Abstract acyclovir Zovirax




J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):289-94.
Liquid chromatographic method for the determination of ganciclovir and/or acyclovir in human plasma using pulsed amperometric detection.

Kishino S, Takekuma Y, Sugawara M, Shimamura T, Furukawa H, Todo S, Miyazaki K.

Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan.

We have developed a simple, rapid and highly sensitive method for determining plasma concentrations of ganciclovir and/or acyclovir by using reversed-phase chromatography followed by pulsed amperometric detection. A linear relationship between the amount of ganciclovir (0.05-10 microg/ml plasma) or acyclovir (0.1-20 microg/ml plasma) and peak height ratio was obtained. The relative standard deviations of all standard curves were greater than or equal to 0.999. The limits of detection for ganciclovir and acyclovir quantitation were 10 ng/ml and 50 ng/ml (signal/noise >3), respectively. Daily fluctuations of plasma standard curves (n=5) for the ganciclovir and acyclovir samples were small, with relative standard deviations (RSD) of 3.3 and 4.5% (n=5), respectively. The intra-assay precision for the ganciclovir and acyclovir samples were 6.9 (n=5) and 5.5% (n=5), respectively. Inter-assay precision of ganciclovir (n=3) and acyclovir (n=3) ranged from 2.6 to 6.8% and 3.5 to 5.0%, respectively. Using this method, the pharmacokinetics and removal of ganciclovir during continuous hemodiafiltration (CHDF) in a liver transplant recipient being treated for severe cytomegalovirus infection was investigated. The mean (+/-SD) ratio of ganciclovir concentrations at the inlet and outlet of the dialyzer (C(outlet)/C(inlet)) was 0.56+/-0.09. The areas under the curves of ganciclovir up to 12 h postdosing (AUC(0-->12)) at the inlet and outlet of the dialyzer were 12.54 microg h/ml and 7.16 microg h/ml, respectively. The ultrafiltrate of ganciclovir was 16.6 mg. The terminal elimination half-life (T(1/2)) of ganciclovir during CHDF was 3.6 h. These results demonstrate that CHDF effectively removes ganciclovir. Until formal guidelines have been established, ganciclovir or acyclovir dosage should be adjusted according to the results of monitoring of plasma drug concentration. The method described here is suitable for clinical monitoring of plasma ganciclovir or acyclovir levels in solid organ transplant recipients and for use in studies involving pharmacokinetics. Copyright 2002 Elsevier Science B.V.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12401354&dopt=Abstract acyclovir Zovirax