G.E. Parry

University of Utah, Salt Lake City, UT, United States

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Publications (4)20.42 Total impact

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    ABSTRACT: The permeation enhancing property of 5% oleic acid in ethanol on -estradiol was investigated in vitro and in vivo using symmetrical and asymmetrical side-by-side diffusion cells and the human skin sandwich flap, respectively. -Estradiol permeability in vitro and in vivo was similar in 75% ethanol (ETOH). Oleic acid (5%) did not alter -estradiol permeability in vivo but increased permeability sixfold in vitro in symmetrical diffusion cells. -Estradiol permeability in oleic acid was not different from that in ETOH, however, using asymmetrical diffusion cells. Stratum corneum-to-vehicle partition coefficients of -estradiol in the vehicles were similar, yet fourfold more steroid was detected in skin biopsies from the in vitro symmetrical diffusion cells. Thus, oleic acid increased -estradiol permeability in vitro only when skin was equilibrated with fatty acid. Attention to in vitro diffusion cell design and its relevance in vivo is critical to defining the mechanisms of enhanced solute permeation.
    Pharmaceutical Research 11/1993; 10(12). · 4.74 Impact Factor
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    ABSTRACT: Clinical experience demonstrates that oral acyclovir (ACV) is superior to topical ACV in treating recurrent cutaneous herpes simplex virus type 1 (HSV-1) infections. Cutaneous HSV-1 infections are complex in their pathology, affecting the basal epidermis in skin as well as establishing a latency phase in sensory ganglia. In vitro and in vivo human skin model systems were used in the present study to quantitate ACV disposition and absorption in skin and blood following two routes of administration and to investigate whether bioavailability differences were the result of insufficient drug delivery. Physiochemical and physiologic parameters determined from these experiments were used to develop a mathematical model to predict ACV disposition and absorption in human subjects. Model predictions and in vivo data agree; topical administration of commercial 5% ACV ointment and cream result in a 48 times greater total epidermal ACV concentration than after oral administration. Mathematical modeling of the ACV concentration gradient through the epidermis revealed, however, that the drug concentration in the target site of HSV-1 infections, the basal epidermis, is 2-3 times less after topical administration than after oral administration. Thus, the observed lack of clinical efficacy with topical ACV therapy in the recurring HSV-1 infection likely reflects the insufficient delivery of the drug to the target site of the HSV-1 infection, the basal epidermis.
    Journal of Investigative Dermatology 07/1992; 98(6):856-63. · 6.19 Impact Factor
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    ABSTRACT: The possibility of predicting the behavior of in vivo systems based on physical and chemical parameters determined by in vitro experiments is examined using benzoic acid. The physical and chemical parameters governing percutaneous absorption of benzoic acid—permeability, partition coefficient, and skin thickness—were determined by in vitro experiments as described in Ref. 1. These parameters were used, in combination with benzoic acid elimination kinetics, to predict the results of in vivo experiments using a comprehensive mathematical model. The in vivo system consists of a congenitally athymic (nude) rat with a surgically constructed human skin sandwich (HSSF) flap on which a donor cell is placed. To apply the in vitro parameters to an in vivo system requires a suitable pharmacokinetic model describing distribution and elimination for benzoic acid in the nude rat. Blood concentrations of benzoic acid following a bolus intravenous injection are closely described by a two-compartment open pharmacokinetic model with elimination occurring from only one compartment. The mathematical model of the rat-donor cell system combines this two-compartment model of the rat with a percutaneous absorption model to provide useful estimates of the measured in vivo blood levels. Comparisons of predicted and measured results suggest that the parameters determined by in vitro experimentation can be used to predict the behavior of complex in vivo systems, if a suitable mathematical model is available.
    Pharmaceutical Research 01/1990; 7(4). · 4.74 Impact Factor
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    ABSTRACT: The percutaneous absorption of benzole acid across human skin in vitro was experimentally and mathematically modeled. Skin partition coefficients were measured over a range of benzoic acid concentrations in both saline and distilled water. The permeation of benzoic acid was measured across isolated stratum corneum, stratum corneum and epidermis, and split-thickness skin. These experiments demonstrated that the stratum corneum was the rate-limiting barrier and that the flux is proportional to the concentration of the undissociated species. The permeation data were analyzed with a comprehensive non-steady-state mathematical model of diffusion across skin. Two adjustable parameters, the effective skin thickness and diffusivity, were fit to the permeation data by nonlinear regression.
    Pharmaceutical Research 01/1990; 7(3). · 4.74 Impact Factor