Maintenance of skin viability during in vitro percutaneous absorption/metabolism studies

Collier, Steven W.; Sheikh, N.; Sakr, Adel; Lichtin, J. L.; Stewart, Raymond F.; Bronaugh, Robert L.

doi:10.1016/0041-008x(89)90159-2

Cited by 117 publications

(46 citation statements)

References 22 publications

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“…The use of cell culture media or other physiologically compatible receptor fluids will increase the duration of metabolic activity. The most widely used indicator of skin viability has been glucose utilization (48) since energy metabolism is critical to metabolic integrity.…”

mentioning

confidence: 99%

Guidance Document for the Conduct of Skin Absorption Studies

2004

OECD Series on Testing and Assessment

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mentioning

confidence: 99%

Guidance Document for the Conduct of Skin Absorption Studies

2004

OECD Series on Testing and Assessment

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“…Testosterone and estradiol were more completely metabolized than the previous two compounds during skin permeation in the rat (9). Approximately 20% of the absorbed estradiol was converted to estrone.…”

Section: Absorption and Metabolism Datamentioning

confidence: 90%

“…Skin metabolism can be studied in combination with skin absorption measurements by using in vitro flow-through diffusion cells (8) with a physiologic buffer as the receptor fluid (9). Viability of the skin can be maintained in diffusion cells for at least 24 hr, as assessed by maintenance of glucose utilization and metabolic activity and by histologic evaluation.…”

Section: Skin Absorption and Metabolism Methodsmentioning

confidence: 99%

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Influence of metabolism in skin on dosimetry after topical exposure.

Bronaugh

Collier

Macpherson

et al. 1994

Environ Health Perspect

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Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[alpyrene and 7-ethoxycoumarin) penetrated human and hairless guinea pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized during absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. Plasma concentrations in the hairless guinea pig were accurately predicted for the model compound, benzoic acid, from in vitro absorption, metabolism, and other pharmacokinetic parameters. -Environ Health Perspect 102(Suppl 1 1): 71-74 (1994)

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“…His research in skin toxicology, with an estimated 43 Pubmed-defined publications, began with Bob Scheuplein [78]. Bob, with many colleagues such as Jeff Yourick, Randy Wickett and Raymond Stewart, has made contributions in skin penetration methodology, including maintaining skin viability for metabolism studies [79] and the better definition of the skin reservoir as a determinant for skin penetration [80]. One of Bob's other great contributions has been the various editions of his book, co-edited with Howard Maibach, on percutaneous absorption that has included substantive reviews, such as that which Yuri Anissimov and I contributed [81].…”

Section: My Generation - the Baby Boomersmentioning

confidence: 99%

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

Roberts¹

2013

Skin Pharmacol Physiol

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An appreciation of solute-vehicle-skin interactions underpins our current understanding of the processes of percutaneous absorption as well as in the prediction of the extent of absorption. This understanding has been reached through principles developed and validated over the last century through the work of a number of authors, including Dale Wurster, Takeru Higuchi, Irvin Blank, Robert Scheuplein, Gordon Flynn, Boyd Poulsen and Tom Franz, as well as by many scientists from my and younger generations. Their work has led to an appreciation of the rate-limiting steps in percutaneous penetration, the role played by the physicochemical properties of the solute, vehicle and skin and the variability that may arise from using various experimental/mathematical/pharmacokinetic models to quantify absorption as well as enabling the prediction of local and systemic efficacy and toxicity. In addition, unexpected behaviour may result from non-ideality in solute-vehicle-skin effects, including dehydration, chemical enhancement, supersaturation, metabolism, sequestration and vascular effects, including those of nanosystems on the local vasculature. In general, in vitro skin penetration profiles are predictive of in vivo profiles but a number of exceptions also exist.

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Maintenance of skin viability during in vitro percutaneous absorption/metabolism studies

Cited by 117 publications

References 22 publications

Guidance Document for the Conduct of Skin Absorption Studies

Guidance Document for the Conduct of Skin Absorption Studies

Influence of metabolism in skin on dosimetry after topical exposure.

Solute-Vehicle-Skin Interactions in Percutaneous Absorption: The Principles and the People

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