Nucleosides Nucleotides Nucleic Acids. 2000 Jan-Feb;19(1-2):471-9.
Synthesis and antiviral evaluation of 1-O-hexadecylpropanediol-3-P-acyclovir: efficacy against HSV-1 infection in mice.

Beadle JR, Kini GD, Aldern KA, Gardner MF, Wright KN, Rybak RJ, Kern ER, Hostetler KY.

Department of Medicine University of California, San Diego, La Jolla 92093-0676, USA.

We synthesized, 1-O-hexadecylpropanediol-3-P-acyclovir, an orally bioavailable lipid prodrug of acyclovir and evaluated it for in vitro and in vivo activity against herpes simplex virus infections. Although 1-O-hexadecylpropanediol-3-P- acyclovir was less active in vitro than acyclovir, on a molar basis it was 2.4 times more active orally in preventing mortality from acute HSV-1 infection in mice. In vitro, 1-O-hexadecylpropanediol-3-P-acyclovir was also more active than acyclovir in a thymidine kinase negative mutant strain of HSV-1 (DM21) and had somewhat higher activity in cytomegalovirus infection in vitro due to it's ability to bypass thymidine kinase.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10772728&dopt=Abstract acyclovir Zovirax




Ther Drug Monit. 1997 Dec;19(6):701-4.
Pharmacokinetics of acyclovir in patients undergoing continuous venovenous hemodialysis.

Boulieu R, Bastien O, Gaillard S, Flamens C.

Universite Claude Bernard Lyon 1, Institut des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacie Clinique, France.

The pharmacokinetics of acyclovir in three patients undergoing continuous venovenous hemodialysis was investigated. Acyclovir was administered as an intravenous infusion over 1 hour at a dose of 5 mg/kg daily in one patient and 10 mg/kg every 48 hours in two patients. Samples from the arterial and venous blood lines and from ultrafiltrate were collected to calculate pharmacokinetic parameters, sieving coefficient and clearance of ultrafiltration. Plasma concentrations of acyclovir were assessed by high-performance liquid chromatography. Peak plasma concentrations were 9.3 mg/l for the patient receiving 5 mg/kg daily, 29.6 mg/l and 20.7 mg/l for the two patients with 10 mg/kg every 48 hours. The elimination half-life ranged from 8.8 to 11.2 hours and was approximately half those found in patients with renal impairment. The clearance by ultrafiltration was from 17.4 to 22.3 ml/minute and reached nearly 35% of the total clearance. The sieving coefficient ranged from 0.92 to 0.98 with an average rate of removal over the dosing interval ranging from 6.7 to 13.0 mg/hour. These data should be taken into account to optimize drug therapy in patients on continuous hemodialysis. Until formal guidelines are defined, acyclovir dosage should be adjusted according to monitoring of plasma drug concentrations.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9421114&dopt=Abstract acyclovir Zovirax




J Infect Dis. 1999 Sep;180(3):594-9.
The comparative effects of famciclovir and valacyclovir on herpes simplex virus type 1 infection, latency, and reactivation in mice.

LeBlanc RA, Pesnicak L, Godleski M, Straus SE.

Medical Virology Section, Laboratory of Clinical Investigation, National Institutes of Health, Bethesda, Maryland 20892-1888, USA.

Infections by herpes simplex virus (HSV) cannot yet be eliminated, but the severity of the disease can be reduced. Two newer drugs with established efficacy for such infections, famciclovir and valacyclovir, were tested in a mouse eye model of HSV infection. Both drugs significantly reduced mortality and titers of virus shed from the eyes of mice infected with an otherwise lethal dose of HSV type 1 (HSV-1). Similar titers of HSV-1 were found in the eyes, ganglia, and brains of treated animals. Although valacyclovir reduced the latent viral DNA load better in these studies than did famciclovir, rates of reactivation by explantation and UV exposure were the same. Thus, in this study, famciclovir and valacyclovir were equally effective in limiting the virulence and spread of HSV-1, despite their biochemical and pharmacologic differences.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10438344&dopt=Abstract acyclovir Zovirax




Hua Xi Yi Ke Da Xue Xue Bao. 1998 Sep;29(3):329-33.
[Preparation of acyclovir-polybutylcyanoacrylate-nanoparticles by emulsion polymerization method]

[Article in Chinese]

Zhang Z, Tian H, He Q.

Department of Pharmaceutics, School of Pharmacy, Chengdu.

The aim of this study was to optimize the conditions and technology of preparing acyclovir-polybutylcyanoacrylate-nanoparticles (ACV-PBCA-NP) which has the diameter of about 100 nm and the shape of a sphere. The influential factors on sphericization were observed by single factor optimization. The preparation conditions and technology were optimized by the even design method. The contents of acyclovirin in acyclovir polybutyloganoacrylate nanoparticles were determined by HPLC. The optimum conditions and technology of preparing acyclovir polybutylcyanoacrylate nanoparticles were decided and put into use. The average diameter of the ACV-PBCA-NP thus prepared was 108.5 +/- 94.8 (n = 588). Its embedding ratio was 71.8%, and drug loading was 18.5%. The results suggest that the conditions and technology of preparing ACV-PBCA-NP presented in this paper are stable and practical.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10684106&dopt=Abstract acyclovir Zovirax




Antimicrob Agents Chemother. 2000 Jan;44(1):30-8.
Efficacies of topical formulations of foscarnet and acyclovir and of 5-percent acyclovir ointment (Zovirax) in a murine model of cutaneous herpes simplex virus type 1 infection.

Piret J, Desormeaux A, Gourde P, Juhasz J, Bergeron MG.

Centre de Recherche en Infectiologie, Universite Laval, Quebec, Quebec, Canada.

The topical efficacies of foscarnet and acyclovir incorporated into a polyoxypropylene-polyoxyethylene polymer were evaluated and compared to that of 5% acyclovir ointment (Zovirax) by use of a murine model of cutaneous herpes simplex virus type 1 infection. All three treatments given three times daily for 4 days and initiated 24 h after infection prevented the development of the zosteriform rash in mice. The acyclovir formulation and the acyclovir ointment reduced the virus titers below detectable levels in skin samples from the majority of mice, whereas the foscarnet formulation has less of an antiviral effect. Reducing the number of treatments to a single application given 24 h postinfection resulted in a significantly higher efficacy of the formulation of acyclovir than of the acyclovir ointment. Acyclovir incorporated within the polymer was also significantly more effective than the acyclovir ointment when treatment was initiated on day 5 postinfection. The higher efficacy of the acyclovir formulation than of the acyclovir ointment is attributed to the semiviscous character of the polymer, which allows better penetration of the drug into the skin.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10602719&dopt=Abstract acyclovir Zovirax