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uams.edu

The purpose of this study is to examine the influence of Azone upon the skin target site free drug concentration (C(*)) and its correlation with the in vivo antiviral efficacies of cidofovir (HPMPC) and acyclovir (ACV) against HSV-1 infections. Formulations of HPMPC and ACV with or without Azone were used. The in vitro skin flux experiments were performed and the C(*) values were calculated. For the in vivo efficacy studies, hairless mice cutaneously infected with HSV-1 were used and three different treatment protocols were carried out. The protocols were chosen based upon when therapy is initiated and terminated in such a way to assess the efficacy of the test drug to cure and/or prevent HSV-1 infections. A finite dose of the formulation was topically applied twice a day for the predetermined time course for each protocol and the lesions were scored on the fifth day. For ACV formulation with Azone, the C(*) values and hence the in vivo efficacy were much higher than those for that without Azone. In protocol #1, however, early treatment did not increase the in vivo efficacy of ACV when compared with the standard treatment protocol #3. In protocol #2 where the treatment was terminated on the day of virus inoculation, the efficacies for both ACV formulations were completely absent. Although the estimated C(*) values for HPMPC formulations with and without Azone were comparable, formulation with Azone was much more effective than that without Azone in all treatment protocols. HPMPC formulations with Azone at similar flux values were much more effective in "treating and preventing" HSV-1 infections than those without Azone. For ACV formulations, in contrast, addition of Azone has failed to show any effect on the preventive in vivo antiviral efficacy and the enhancement of ACV in vivo antiviral efficacy was merely the skin permeation enhancement effect of Azone.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12593946&dopt=Abstract

fhcrc.org

Herpes simplex virus (HSV) commonly reactivates after stem-cell transplantation (SCT), despite acyclovir prophylaxis. Whether HSV-seropositive recipients with HSV-seronegative or type-discordant donors had more frequent and severe HSV infections than those with HSV type-concordant donors was explored. Banked serum samples from HSV-positive SCT recipients and their donors were tested for the presence of HSV antibodies. HSV-1-positive SCT recipients from HSV-1-negative donors had more frequent and longer episodes than HSV-1-positive SCT recipients from HSV-1-positive donors; the proportion of patients receiving antiviral treatment for >10% of follow-up days was 27.4% versus 7.2% (P<.001). Both HSV-1 visceral infection (9.8% vs. 2.2%; P=.001) and acyclovir resistance (5.8% vs. 1.8%; P=.03) were more common in type-discordant than -concordant patients, respectively; these associations were confirmed in multivariable models. Serological testing of donors can identify patients who are at highest risk for HSV-related morbidity, for whom prolonged prophylaxis or donor vaccination (once available) could be considered.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12599054&dopt=Abstract




Antimicrob Agents Chemother. 2003 Mar;47(3):991-6.
Pharmacokinetics of intravenous acyclovir, zidovudine, and acyclovir-zidovudine in pregnant rats.

Brown SD, Bartlett MG, White CA.

Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens 30602-2352, USA.

The pharmacokinetics and placental transfer of acyclovir and zidovudine monotherapies and acyclovir-zidovudine combination therapy were compared in the pregnant rat. Timed-pregnancy Sprague-Dawley rats were used for the study. Doses of 60 mg of each drug/kg of body weight in monotherapy and in combination therapy were given by intravenous bolus, and samples of maternal plasma, amniotic fluid, fetal tissue, and placental tissue were collected over a period of 8 h postdose. Concentrations of each drug in the various matrices were measured by high-performance liquid chromatography. All data were analyzed by using WinNonlin. A one-compartment model with first-order elimination was used to fit the AZT plasma data from the combination therapy rats, but the plasma data from the other groups were fit to a two-compartment model. Tissue data were analyzed by noncompartmental analysis to generate area-under-the-concentration-time-curve values. Implementation of the combination therapy altered the pharmacokinetics of each drug compared to its monotherapy pharmacokinetics. The combination of these two drugs may potentiate fetal and amniotic fluid exposures to each drug.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12604532&dopt=Abstract












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