Estimation of the acyclovir concentration in the epidermis following transdermal drug delivery and its correlation with its antiviral efficacy

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Title Estimation of the acyclovir concentration in the epidermis following transdermal drug delivery and its correlation with its antiviral efficacy
Publication Type thesis
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Song, Wei-qi
Date 1989-12
Description An experimental animal model for the study of the antiviral efficacy of acyclovir (ACV) in cutaneous HSV-1 infections utilizing controlled drug delivery with transdermal patches in hairless mice was developed previously. In this model, the extent of virus induced lesion development in skin areas underneath and/or adjacent to the areas covered by the dermal patches was used, in order to evaluate the topical and systemic antiviral efficacy of the patches. Both efficacies were expressed as a function of the drug delivery rate of the dermal patches. In the present study, the drug concentration in the epidermis/ dermis interface for both topical and systemic drug delivery was estimated. In the case of topical delivery, the drug concentration was deduced from the flux equation for ACV transport across Azone pretreated hairless mouse skin, assuming a permeability coefficient of the dermis corresponding to its full anatomical thickness. In the case of systemic delivery, the drug concentration in the water compartment of the epidermis was obtained from pharmacokinetic studies, which provided steady state blood levels of ACV following dermal patch application with hairless mice. For the equal topical and systemic antiviral efficacy values, the topical drug concentration was found to be 40 times higher than the systemic drug concentration. The reason for this difference was sought in the effect of the blood flow on the effective thickness of the dermis as a transport barrier in vivo. Estradiol was used as a probe in these studies. The transdermal permeation of estradiol and its main metabolite, estrone, was studied in vitro and in vivo using estradiol dermal patches. The experimentally obtained fluxes were fitted to a previously developed computational model for simultaneous transport and metabolism of estradiol in skin, and the effect of a reduced effective dermis thickness was tested. Different assumptions regarding the location of metabolic enzyme in the skin and the diffusivities in the basal and the keratinized epidermal layers were employed in this model, in order to explain the differences in the estrone back flux between the in vitro and the in vivo experiments. It was shown that a 40-fold reduction of the effective dermis thickness due to the blood flow in vivo was consistent with the experimental data.
Type Text
Publisher University of Utah
Subject Pharmacokinetics; Drug therapy
Subject MESH Acyclovir; Administration, Cutaneous; Antiviral Agents; Biological Transport; Drug Delivery Systems; Herpesviridae Infections; Skin Absorption
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "Estimation of the acyclovir concentration in the epidermis following transdermal drug delivery and its correlation with its antiviral efficacy. " Spencer S. Eccles Health Sciences Library.
Rights Management © Wei-qi Song.
Format application/pdf
Format Medium application/pdf
Format Extent 1,320,912 bytes
Identifier undthes,3880
Source Original University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 1,321,055 bytes
ARK ark:/87278/s67s7qj4
Setname ir_etd
ID 190992
Reference URL https://collections.lib.utah.edu/ark:/87278/s67s7qj4
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