hc-sc.gc.ca

PURPOSE: To evaluate the use of a flow-through diffusion cell system to assess the absorption and penetration characteristics of drug (acyclovir) products. METHODS: In vitro studies were performed to assess the absorption/penetration of acyclovir using a flow-through diffusion cell system with human skin sections obtained from 19 healthy women following mammoplasty. The skin sections, 200-400 microm thick, were prepared using a dermatome. Acyclovir ointment (approximately 10 mg) spiked with (3)H-labelled acyclovir was applied onto the stratum corneum/epidermis side. The skin sections were continually perfused on the dermis side with sterilized culture medium, Buffered Hanks' Balanced Salt Solution, saturated with a CO(2)/O(2) (5/95%). RESULTS: After 24 hours, the percentages of acyclovir-derived radioactivity (based on dose applied) in different components were as follows: stratum corneum (SC), 0.20+0.28; viable skin (VS), 0.40+0.38; effluent fluid (EF), 0.25+0.53. A second set of experiments was performed using tape stripped (10X) skin sections. Levels of acyclovir-derived radioactivity were VS, 1.21+1.43 and EF, 2.65+2.61, which were threefold higher (p < 0.05) for VS and elevenfold higher (p < 0.05) for EF compared to the results obtained with the intact skin sections. CONCLUSIONS: The SC is the main barrier layer for the penetration of acyclovir through human skin. The use of the flow-through diffusion cell system provides an appropriate in vitro model to assess the absorption/penetration of acyclovir through human skin layers and therefore can potentially be used for dermal formulation characterization and development.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10948397&dopt=Abstract acyclovir Zovirax




J Pharm Biomed Anal. 1998 Oct;18(1-2):249-54.
Determination and pharmacokinetics of acyclovir after ingestion of suspension form.

Jankowski A, Jankowska AL, Lamparczyk H.

Medical Center of Postgraduate Education, Department of Biopharmaceutics, Bydgoszcz, Poland.

The study describes, simple, precise, sensitive and accurate HPLC assay with spectrofluorimetric detection for the determination of acyclovir in human plasma. The method was linear over a range 25 1200 ng ml(-1). The average yield in this method exceeded 80%. Limits of quantitation and detection were 25 and 10 ng ml(-1), respectively. On the basis of reported method, a single-dose of pharmacokinetics on 24 men, in two doses (200 and 400 mg) of acyclovir suspension has been investigated. Pharmacokinetic parameters obtained from both doses of the drug were compared. The linearity of acyclovir pharmacokinetics in the investigated dose ranges has been confirmed.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9863965&dopt=Abstract acyclovir Zovirax




Drug Metab Dispos. 1994 Jan-Feb;22(1):55-9.
Metabolic fate and pharmacokinetics of the acyclovir prodrug valaciclovir in cynomolgus monkeys.

de Miranda P, Burnette TC.

Division of Experimental Therapy, Burroughs Wellcome Co., Research Triangle Park, NC 27709.

Valaciclovir, the L-valyl ester of acyclovir (ZOVIRAX), demonstrated good oral absorption and nearly complete conversion to acyclovir in cynomolgus monkeys, indicating its suitability as an orally administered prodrug. The major urinary metabolites of [8-14C]valaciclovir, administered orally (10 and 25 mg/kg) or intravenously (10 mg/kg) to male monkeys, were acyclovir (46%-59% of urinary radioactivity), 8-hydroxyacyclovir (25%-30%), and 9-(carboxymethoxymethyl)guanine (CMMG) (11%-12%). Following oral and intravenous dosing, intact prodrug accounted for only 0.5% and 6% of urinary radioactivity, respectively. Dose-independent kinetics were observed for acyclovir derived from orally administered [8-14C]valaciclovir at the 10 and 25 mg/kg dose levels, with both AUC (24 and 60 microM.hr, respectively) and Cmax (8 and 23 microM, respectively) increasing nearly in proportion to the dose. Acyclovir was present in plasma at all sampling times (5 min to 7 hr postdose) after both oral doses, whereas the prodrug was not detected following either oral dose. The elimination of acyclovir after oral administration was monophasic, with an apparent half-life of 1.3-1.5 hr. Similar to acyclovir, both 8-hydroxyacyclovir and CMMG demonstrated dose-independent kinetics with apparent elimination half-lives of 1-1.6 hr. Intravenously administered [8-14C]valaciclovir (10 mg/kg) was rapidly converted to acyclovir, with the elimination half-life of acyclovir (0.9 hr) being 1.5-fold that of the prodrug (0.6 hr). The oral bioavailability of acyclovir derived from valaciclovir in cynomolgus monkey was 67 +/- 13%, representing a significant improvement over the limited bioavailability after acyclovir administration to primates.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8149890&dopt=Abstract acyclovir Zovirax




Ann Otol Rhinol Laryngol. 1999 May;108(5):423-8.
Therapy of idiopathic sudden sensorineural hearing loss: antiviral treatment of experimental herpes simplex virus infection of the inner ear.

Stokroos RJ, Albers FW, Schirm J.

Department of Otorhinolaryngology, University Hospital Groningen, The Netherlands.

Experimental herpes simplex virus type 1 (HSV-1) labyrinthitis provides a model of idiopathic sudden sensorineural hearing loss (ISSHL). Corticosteroids improve the prognosis for hearing recovery in ISSHL, but the effects of acyclovir are unknown. To establish the therapeutic efficacy of acyclovir (Zovirax) and prednisolone in experimental HSV-1 viral labyrinthitis, we induced HSV-1 labyrinthitis in 12 guinea pigs. Three animals received no treatment, 3 received prednisolone, 3 received acyclovir, and 3 received both. Four other animals served as controls, receiving culture medium only. Hearing, HSV-1 antibody titers, and cochlear damage were evaluated. The HSV-1 labyrinthitis caused hearing loss within 24 hours. Combination treatment consisting of prednisolone and acyclovir resulted in earlier hearing recovery and less extensive cochlear destruction compared to prednisolone or acyclovir as a monotherapy. The beneficial effect of this treatment modality remains to be demonstrated in ISSHL.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10335700&dopt=Abstract acyclovir Zovirax




Clin Infect Dis. 1998 Jan;26(1):85-90.
Acyclovir use and survival among human immunodeficiency virus-infected patients with CD4 cell counts of < 500/mm3. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA).

Torres RA, Neaton JD, Wentworth DN, Barr MR, Abrams D, Sherer R, Ward T, Sampson J.

AIDS Center, St. Vincent's Hospital and Medical Center of New York, New York 10011, USA.

To examine the relationship between acyclovir use and survival in AIDS, we performed a retrospective analysis of data collected through an observational cohort of the 17-site Community Program for Clinical Research on AIDS (CPCRA), under the sponsorship of the National Institute of Allergy and Infectious Diseases. Data were analyzed regarding 2,368 patients with CD4+ lymphocyte counts of < 500/mm3, and 7,836 follow-up visits were conducted from September 1990 to July 1994. Factors associated with use of acyclovir were studied by stratified analysis of variance and Mantel-Haenzel chi 2 tests. The association between acyclovir and survival was studied with use of the proportional hazards regression model. Individuals reporting acyclovir use were more likely to be white, male, and homosexual; to have a history of herpes simplex and zoster; and to have lower CD4+ T cell counts than those who did not. After adjustments for differences in baseline factors, acyclovir use was not associated with prolonged survival.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9455514&dopt=Abstract acyclovir Zovirax