J Neurol Neurosurg Psychiatry. 1997 Sep;63(3):321-6.
Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome.

McGrath N, Anderson NE, Croxson MC, Powell KF.

Department of Neurology, Auckland Hospital, New Zealand.

OBJECTIVES: The frequency and characteristics of the long term sequelae of herpes simplex encephalitis were assessed after treatment with acyclovir. METHODS: Patients were included if they were treated with acyclovir and the diagnosis of herpes simplex encephalitis was confirmed by culture of herpes simplex virus (HSV) from the brain, an increase in the CSF HSV antibody titre, or detection of HSV deoxyribonucleic acid in the CSF. Each patient's medical records were reviewed and surviving patients were interviewed and examined. RESULTS: A diagnosis of herpes simplex encephalitis was confirmed in 42 patients. Five patients (12%) died in the first month. Three patients (7%) had severe neurological sequelae and died after a longer interval. All but one of the 34 surviving patients had neurological symptoms, an abnormal neurological examination, or both. Twenty patients (48%) performed everyday activities as well as before herpes simplex encephalitis; nine patients (21%) were living independently, but were functioning at a lower level than before the illness; and five patients (12%) had a severe neurological deficit. Twenty nine of the 34 survivors were assessed six months to 11 years after herpes simplex encephalitis. The most common long term symptoms were memory impairment (69%), personality and behavioural abnormalities (45%), and epilepsy (24%). Short term memory impairment (70%), anosmia (65%), and dysphasia (41%) were the most common signs. CONCLUSIONS: Although acyclovir has reduced the mortality of herpes simplex encephalitis, 30% of this group of patients either died or had a severe neurological deficit. The other 70% of the patients regained independence in activities of daily living, but most of these people had persistent neurological symptoms, signs, or both.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9328248&dopt=Abstract acyclovir Zovirax

mwu.mukogawa-u.ac.jp

The effect of cyclosporine A (CyA) on the pharmacokinetics of acyclovir in neonatal and adult rats was studied. CyA at 25 and 50 mg/kg for 2-week-old and adult rats, respectively, given as a subcutaneous injection, reduced growth of the 2-week-old rats and inhibited growth of adult rats. The plasma concentration of acyclovir after intravenous administration (20 mg/kg) to neonatal CyA-treated rats increased and the total body clearance decreased compared with the neonatal controls. The bioavailabilities of acyclovir for neonatal control and CyA-treated rats after oral administration were significantly different at 15.6 and 22.0%, respectively, but those for the adult control and CyA-treated rats were the same at 15.6 and 14.0%, respectively. Experiments using the everted sac method showed that the amount of acyclovir transferred was higher in neonatal CyA-treated rats than the controls, but there was no difference in adult rats. A good relationship was observed between the bioavailabilities (in vivo) and cumulative transferred amounts (in vitro) in CyA-treated and control rats. Lactase activity in the brush border membrane of the intestine in the neonatal CyA-treated rats was significantly higher than in the controls. These results suggest that the gastrointestinal maturation of CyA-treated neonates is suppressed, resulting in increased bioavailability of acyclovir, while the gastrointestinal absorption of acyclovir does not differ between adult CyA-treated and control rats.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9691165&dopt=Abstract acyclovir Zovirax




Antiviral Res. 1999 Jan;40(3):155-66.
Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants.

Ida M, Kageyama S, Sato H, Kamiyama T, Yamamura J, Kurokawa M, Morohashi M, Shiraki K.

Department of Virology, Toyama Medical and Pharmaceutical University, Sugitani, Japan.

We have characterized the differential actions of acyclovir and penciclovir against varicella-zoster virus (VZV) in cell culture by comparing the frequency of appearance of resistant viruses followed by their characterization. Cells were infected with cell-free virus and the cultures were successively treated with increasing concentrations of acyclovir or penciclovir. Drug-resistant viruses were selected in the presence of 6 microg/ml of acyclovir or penciclovir. The emergence frequency of resistant viruses was significantly higher following acyclovir exposure than following penciclovir exposure (Fisher's exact test, P<0.0001), possibly reflecting virus growth differences under these experimental conditions. Based on antiviral drug susceptibility and thymidine kinase (TK) activity assays, 11 acyclovir-resistant variants from seven experiments using three virus strains (Kawaguchi strain, Oka varicella vaccine strain and a clinical isolate from a zoster patient) were found to be TK-deficient. Sequence analysis of TK-deficient variants of the Kawaguchi strain revealed deletions that caused frameshifts, resulting in premature termination in the TK gene.

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J Virol Methods. 1996 Jan;56(1):3-11.
Comparison of a DNA probe assay with the plaque reduction assay for measuring the sensitivity of herpes simplex virus and varicella-zoster virus to penciclovir and acyclovir.

Standring-Cox R, Bacon TH, Howard BA.

SmithKline Beecham Pharmaceuticals, Betchworth Surrey, UK.

A DNA probe assay was compared with the plaque reduction assay to determine the sensitivity of clinical isolates of herpes simplex virus (HSV) and varicella-zoster virus (VZV) to penciclovir and acyclovir in MRC-5 cells. In both assays, penciclovir and acyclovir shared comparable activity against cell-free virus (CFV) preparations of VZV and herpes simplex virus type 1 (HSV-1) isolates, whilst acyclovir was significantly more active than penciclovir against herpes simplex virus type 2 (HSV-2) isolates in both the DNA probe assay (P < or = 0.01) and the plaque reduction assay (P < or = 0.01). However, the 50% effective concentrations (EC50s) were generally lower in the DNA probe assay and the correlation between the plaque reduction and DNA probe assays was poor for either compound. Six acyclovir-resistant strains of HSV-1 derived in cell culture were also tested for susceptibility to penciclovir and acyclovir, in the DNA probe and plaque reduction assays. The relative susceptibilities of these strains were comparable, for example, one ACV-resistant strain was susceptible to penciclovir in both assays. Further comparisons of the assay methods were made using cell-associated VZV (CAV). As with CFV the EC50s were significantly lower in the DNA probe assay than the plaque reduction assay for penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). In the DNA probe assay there was no significant difference in the EC50s for either penciclovir or acyclovir when comparing CAV with CFV. However, in the plaque reduction assay the EC50s for CAV were significantly higher than those for CFV for both penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). Overall the DNA probe assay is objective, does not require prior titration of isolates and provides opportunities for automation. It is more suitable for sensitivity testing of large numbers of clinical isolates than the well-established plaque reduction assay.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8690764&dopt=Abstract acyclovir Zovirax




Arch Dermatol. 2001 Sep;137(9):1153-8.
Comparison of new topical treatments for herpes labialis: efficacy of penciclovir cream, acyclovir cream, and n-docosanol cream against experimental cutaneous herpes simplex virus type 1 infection.

McKeough MB, Spruance SL.

Department of Medicine, School of Medicine, Room 4B319, University of Utah, 50 North Medical Dr, Salt Lake City, UT 84132, USA.

BACKGROUND: There are 3 new topical treatments for herpes labialis that have either been approved by the US Food and Drug Administration (penciclovir cream [Denavir] and n-docosanol cream [Abreva]) or recently undergone extensive clinical evaluation (acyclovir cream). The relative efficacy of these products is unknown. OBJECTIVE: To compare the efficacy of penciclovir cream, acyclovir cream, n-docosanol cream, and acyclovir ointment in an experimental animal model of cutaneous herpes simplex virus type 1 (HSV-1) disease. DESIGN: The backs of guinea pigs were infected with HSV-1 using a vaccination instrument. Active treatments and corresponding vehicle controls were applied for 3 to 5 days beginning 24 hours after inoculation. MAIN OUTCOME MEASURES: After completion of treatment, the animals were killed and the severity of the infection assessed from the number of lesions, the total lesion area, and the lesion virus titer. RESULTS: Penciclovir cream effected modest reductions in lesion number (19%), area (38%), and virus titer (88%) compared with its vehicle control, and each of these differences was significantly greater (P<.05) than the reductions effected by acyclovir ointment (0%, 21%, and 75%, respectively). The acyclovir cream effect (reductions of 4%, 28%, and 77%, respectively) was less than that of penciclovir cream, and this difference was confirmed by 2 additional head-to-head experiments. Two experiments with n-docosanol cream failed to show statistically significant differences by any parameter between n-docasonol cream and vehicle control-treated sites or between n-docosanol and untreated infection sites. CONCLUSIONS: In this model, the efficacy of penciclovir cream was greater than acyclovir cream, acyclovir cream was greater than or equal to acyclovir ointment, and acyclovir ointment was greater than n-docosanol cream. Since our model was designed to evaluate compounds that function primarily through antiviral activity, the negative findings with n-docosanol in these studies do not exclude that it might work clinically through other mechanisms.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11559210&dopt=Abstract acyclovir Zovirax