Antiviral Res. 1994 Dec;25(3-4):185-92.
Treatment of acyclovir-unresponsive cutaneous herpes simplex virus infection with topically applied SP-303.

Safrin S, McKinley G, McKeough M, Robinson D, Spruance SL.

Department of Medicine, University of California San Francisco, USA.

The naturally occurring polyphenolic biopolymer SP-303 has in vitro activity against both HSV-1 and HSV-2, including strains that are resistant to acyclovir. Nine AIDS patients with acyclovir-unresponsive mucocutaneous herpes simplex virus infection were treated with thrice daily topical SP-303T ointment in an open-label pilot study. Although a transient decrease in lesion size was observed in 4 patients during study drug therapy, and 3 patients sustained a quantitative decrease in virus burden, neither complete healing nor cessation of virus shedding occurred in any patient. Seven patients complained of pain or burning upon application of the study ointment, causing 1 patient to terminate the study. In summary, application of SP-303T ointment effected no significant improvement in the clinical course of 9 AIDS patients with acyclovir-unresponsive HSV infection.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7710268&dopt=Abstract acyclovir Zovirax




Microbiol Immunol. 1994;38(2):109-15.
Effect of BV-araU and acyclovir on varicella-zoster virus replication with various length and timing of drug exposure.

Machida H, Nishitani M, Ashida N.

Biology Laboratory, R & D Division, Yamasa Corporation, Chiba, Japan.

We studied antiviral effects of 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]uracil (BV-araU) and acyclovir against varicella-zoster virus (VZV) multiplication varying the length or timing of drug exposure. First, residual anti-VZV effect of drugs, exposed to cells for various periods followed by incubation in drug-free medium, was determined by the plaque inhibition assay. None of the drugs showed activity when removed within 24 hr of incubation. Weakened efficacy of BV-araU was seen in 2 days of treatment. When it was removed after 3 or 4 days, the ED50 was as low as that for cultures in which the drug was not removed. Still, plaque inhibition was not complete even at high concentrations. Acyclovir inhibited plaque formation only by 50% or less in 2 days of treatment. It gave a much higher ED50 in 3 days of treatment than that observed without drug removal. In the experiments, in which BV-araU was added to VZV-infected cells 1 day after infection, BV-araU immediately suppressed increase in the number of infective centers at a concentration of 0.001 microgram/ml, and reduced it at concentrations of 0.01 microgram/ml or higher. The reduction of infective centers was seen with a dose-dependent manner when added 2 or 3 days after infection. BV-araU stimulated the decrease in the number of infective centers when added 4 days after infection. This inhibitory effect of acyclovir was very weak. Microscopic observations supported the above results. BV-araU was still much superior to acyclovir in the anti-VZV effect when the length and timing of drug exposure were varied.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8041297&dopt=Abstract acyclovir Zovirax




Arch Dis Child. 1994 Dec;71(6):529-31.
A survey of recommendations given to patients going home after bone marrow transplant.

Brandt L, Broadbent V.

Paediatric Oncology Unit, Addenbrooke's Hospital, Cambridge.

A postal questionnaire was sent to 11 UK Children's Cancer Study Group bone marrow transplant centres asking them for details of their instructions to patients on discharge after either allogeneic or auto transplant; nine centres responded. There was no recommendation on which they all agreed. Though all centres gave prophylactic septrin, the times of starting and stopping treatment varied considerably. Three centres recommended lifelong penicillin after total body irradiation, one treated for two years and five gave no such prophylaxis. Four of nine centres gave routine acyclovir for herpes simplex prophylaxis. Most centres suggested prophylaxis against varicella after contact exposure for one year. However, three gave zoster immune globulin alone, one gave this together with acyclovir, and five gave acyclovir alone. No two centres recommended the same dose of acyclovir. Vaccinations were allowed from 6-18 months after transplant. One centre required documentation of recovery of immune function first. Four centres recommended a child stay off school for six months; others had 'common sense' approaches. Only one centre did not allow family holidays for the first six months but many imposed restrictions on these holidays. Dietary restrictions varied greatly between centres. It is concluded that there is a need for unified and scientifically justified guidelines after transplant for paediatric bone marrow transplant patients.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7726614&dopt=Abstract acyclovir Zovirax




Transplantation. 1998 Dec 27;66(12):1780-6.
Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy.

Turgeon N, Fishman JA, Basgoz N, Tolkoff-Rubin NE, Doran M, Cosimi AB, Rubin RH.

Transplantation and Infectious Disease Units, Massachusetts General Hospital, Boston 02114, USA.

BACKGROUND: Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. METHODS: From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. RESULTS: Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. CONCLUSIONS: Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9884276&dopt=Abstract acyclovir Zovirax




Pharm Res. 1997 Jan;14(1):56-62.
In vivo evaluation of acyclovir prodrug penetration and metabolism through rat skin using a diffusion/bioconversion model.

Bando H, Sahashi M, Yamashita F, Takakura Y, Hashida M.

Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, Japan.

PURPOSE: In order to evaluate the in vivo penetration of prodrugs which undergo metabolism in skin, we analyzed the in vivo penetration profiles of acyclovir prodrugs based on a two-layer skin diffusion model in consideration of metabolic process. METHODS: Acyclovir prodrugs (e.g., valerate, isovalerate and pivarate) were used as model prodrugs and the amounts excreted in urine were measured after percutaneous application. In vivo penetration profiles were then estimated by employing a deconvolution method and the penetration of acyclovir prodrugs was analyzed using a diffusion model. Subsequently, diffusion, partitioning and metabolic parameters were compared under in vitro and in vivo conditions. RESULTS: Although total penetration amounts at the end of the experiment were similar for the three prodrugs, the ratio of intact prodrug to total penetration amount differed significantly. Moreover, the excretion and absorption profiles were also very different for each prodrug. Enzymatic hydrolysis rate constants calculated under in vivo conditions were considerably larger than those obtained in the skin homogenate and in vitro penetration experiments. CONCLUSIONS: The present skin diffusion/bioconversion model combined with computer analysis enables us to comprehensively account for diffusion, partitioning and metabolism during in vivo percutaneous absorption. Nevertheless, different enzymatic hydrolysis rate constants obtained under both in vivo and in vitro conditions demonstrate the difficulty of obtaining accurate values for in vivo enzymatic activity from related in vitro experiments.

Online pharmacy ref source - acyclovir: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9034221&dopt=Abstract acyclovir Zovirax