Curr Treat Options Neurol. 2000 Sep;2(5):407-416.
Bell's Palsy and Herpes Zoster Oticus.

Morrow MJ.

Hattiesburg Clinic, 415 South 28th Street, Hattiesburg, MS 39401, USA.

Normal facial movement is required for chewing, swallowing, speaking, and protecting the eye. Bell's palsy causes most cases of acute, unilateral facial palsy; infection with herpes simplex virus (HSV) type 1 may be its major cause. Varicella zoster virus (VZV) reactivation (Ramsay Hunt syndrome) is less common, but may appear without skin lesions in a form indistinguishable from Bell's palsy. Symptoms improve in nearly all patients with Bell's palsy, and most patients with Ramsay Hunt syndrome, but many are left with functional and cosmetic deficits. Steroids are frequently used to optimize outcomes in Bell's palsy, but proof of their effectiveness is marginal. Oral prednisone has been studied extensively, although some reports have suggested a higher recovery rate with intravenous steroids. Given the existing data, we support the use of oral prednisone in those patients with complete facial palsy, and no contraindications to their use (Fig. 1). In this author's opinion, the greatly increased cost and inconvenience of intravenous steroids cannot be justified by the data available. Antiviral agents may also be effective in treatment of Bell's palsy; HSV is susceptible to acyclovir and related agents. There have been few investigations of acyclovir treatment in Bell's palsy, but one controlled study showed added benefit when the drug was used with prednisone. The risk and cost of acyclovir is low enough that we support its use, with oral steroids, in those patients with complete facial paralysis. Several small studies have implied that oral acyclovir improves the outcome of facial palsy for patients with Ramsay Hunt syndrome. Although these studies do not prove efficacy, evidence for the benefits of antiviral agents in other forms of zoster is strong enough to recommend their use when the facial nerve is involved. VZV is less sensitive to acyclovir than HSV, so higher doses are recommended to treat Ramsay Hunt syndrome. Because some Ramsay Hunt syndrome patients with partial facial palsy do not fully recover, we recommend oral antiviral agents in all patients suspected of having zoster. There is weak evidence to suggest additional benefit of oral steroids in facial zoster, and their use can be supported in immunocompetent individuals. Facial nerve decompression surgery for Bell's palsy and herpes zoster oticus has experienced varying levels of enthusiasm over the years. Recent work implies that early, extensive decompression of the nerve through a middle fossa craniotomy may benefit patients at high risk for persistent deficits. However, until this procedure is subjected to a rigorous, controlled trial comparing it with maximal medical therapy, it is difficult to justify the very high costs and risk.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11096766&dopt=Abstract acyclovir Zovirax[PubMed - as supplied by publisher]




Clin Infect Dis. 2001 Dec 15;33(12):2061-7. Epub 2001 Nov 08.
Clinical and virologic characterization of acyclovir-resistant varicella-zoster viruses isolated from 11 patients with acquired immunodeficiency syndrome.

Saint-Leger E, Caumes E, Breton G, Douard D, Saiag P, Huraux JM, Bricaire F, Agut H, Fillet AM.

Department of Virology, La Pitie-Salpetriere Hospital (Assistance Publique-Hopitaux de Paris), 75651 Paris Cedex, France.

We studied the clinical resistance to acyclovir of infections with varicella-zoster viruses (VZV) in patients with acquired immunodeficiency syndrome, and we correlated it to virologic analyses. Eleven patients with VZV infections (treated with acyclovir, 30 mg/kg/day, given intravenously, or 4 g/day, given orally) were included in the study because of the failure of 10 days of acyclovir therapy. Susceptibility of VZV isolates to acyclovir was tested using a plaque reduction assay to determine the 50% inhibitory concentration (IC(50)) of acyclovir and the SI(50) (IC(50) of the patient isolate/IC(50) of the reference strain) to acyclovir. The thymidine kinase (TK) gene, which supports the resistance, was sequenced on amplified products. Only 3 patients had a significant increase in the IC(50), as compared with the IC(50) of the reference strain (SI(50) of > or =4), and a mutation in the TK gene. For the other 8 patients, the clinical resistance was not confirmed by the virologic results: the SI(50) was < 4, and no mutation was detected in the TK gene. Because no acyclovir-resistant strain appeared during a shorter period of time, we suggest an increase in the duration of the treatment to 21 days before acyclovir resistance is suspected.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11702291&dopt=Abstract acyclovir Zovirax




J Pharm Biomed Anal. 1996 Oct;15(1):39-47.
The preparation, characterisation and solubility characteristics of a hydrogen-bonded complex between acyclovir and cytosine.

Newby CS, Coke M.

Reckitt & Colman Pharmaceuticals, Hull, UK.

Acyclovir and cytosine form a Crick-Watson hydrogen-bonded complex in dimethylsulphoxide (DMSO). For the complex formation Acyclovir + cytosine reversible complex the equilibrium constant, K, was determined using NMR spectroscopy to be K = 1.00 +/- 0.07 mol-1 dm3 at 21 degrees C in DMSO. The acyclovir-cytosine complex was formed in DMSO, then diluted with octan-1-ol to leave a 95.3% v/v octan-1-ol/47% v/v DMSO solution, and demonstrated a 12-fold increase in the saturated solubility of acyclovir. This was compared to a solution of acyclovir alone treated in the same manner. This suggests that a complex species of acyclovir with cytosine has a greater lipophilic character than acyclovir alone. Attempts to increase the octan-1-ol/water partition coefficient for acyclovir produced no significant increase with the presence of cytosine. It was argued that no complexation would occur in water due to the rapid exchange of the protons that are involved in the hydrogen-bonded complex. Experiments to isolate the solid acyclovir-cytosine Crick-Watson hydrogen-bonded complex were performed. Spectra and T1 relaxation times obtained during subsequent solid-state 13C NMR experiments provided evidence that a solid complex can be isolated.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8895075&dopt=Abstract acyclovir Zovirax




J Biol Chem. 1995 Jun 30;270(26):15827-31.
Purification and characterization of a rat liver enzyme that hydrolyzes valaciclovir, the L-valyl ester prodrug of acyclovir.

Burnette TC, Harrington JA, Reardon JE, Merrill BM, de Miranda P.

Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709, USA.

Valaciclovir is an oral prodrug of the antiherpetic agent acyclovir. An enzyme that hydrolyzes valaciclovir to acyclovir, valaciclovir hydrolase (VACVase), was purified from rat liver and characterized. VACVase was a basic (pI 9.4) protein associated with mitochondria. It was monomeric and had a molecular mass of 29 kDa. Amino acid sequences of six VACVase peptides, including its NH2 terminus (13 amino acids) and accounting for approximately 20% of its complete sequence, were not found in the SwissProt protein data base. VACVase hydrolyzed other amino acid esters of acyclovir in addition to valaciclovir (kcat/Km = 58 mM-1 s-1), with a preference for the L-alanyl (kcat/Km = 226 mM-1 s-1) and L-methionyl (kcat/Km = 200 mM-1 s-1) esters. It did not hydrolyze other types of esters or numerous di- and tripeptides and aminoacyl-beta-naphthylamides. Hydrolysis of valaciclovir by VACVase was not inhibited by amastatin, antipain, aprotinin, bestatin, chymostatin, E-64, EDTA, ebelactone A, ebelactone B, elastatinal, leupeptin, pepstatin, or phosphoramidon. It was neither inhibited nor activated by Ca2+, Co2+, Mg2+, Mn2+, or Zn2+. Therefore, this enzyme is not a typical esterase or peptidase and, to our knowledge, it has not been described previously. Its physiological function is not known; however, it may play a significant role in the biotransformation of valaciclovir to acyclovir.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7797586&dopt=Abstract acyclovir Zovirax




J Infect Dis. 1994 Jul;170(1):68-75.
Phenotypic and genotypic characterization of acyclovir-resistant varicella-zoster viruses isolated from persons with AIDS.

Boivin G, Edelman CK, Pedneault L, Talarico CL, Biron KK, Balfour HH Jr.

Dept. of Laboratory Medicine and Pathology, Minneapolis, MN 55455-0392.

Phenotypic and genotypic analyses were done on 17 varicella-zoster virus (VZV) isolates recovered from 10 persons with AIDS (mean CD4 cell count, 16.4/mm3) who had chronic VZV lesions. Eleven acyclovir-resistant isolates were recovered from 10 patients after a mean of 20.1 weeks of therapy. Six susceptible isolates were recovered before acyclovir treatment (n = 1), early during therapy (n = 4; mean time, 4.2 weeks), or after discontinuation of acyclovir (n = 1). Acyclovir-resistant VZV isolates were deficient in thymidine kinase (TK) or induced a TK with altered substrate specificity; all isolates were susceptible to foscarnet. Ten of 11 acyclovir-resistant mutants contained tk gene mutations, including single nucleotide substitutions in highly conserved binding sites (n = 2) as well as nucleotide deletions (n = 4) and insertions (n = 4). These findings suggest that multiple, nonuniform mutations within the tk gene are associated with acyclovir-resistant VZV phenotypes.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8014522&dopt=Abstract acyclovir Zovirax