Comparativein VitroSkin Absorption and Metabolism of Coumarin (1,2-Benzopyrone) in Human, Rat, and Mouse

Beckley-Kartey, Senam A.J.; Hotchkiss, Sharon A.M.; Capel, Margred

doi:10.1006/taap.1997.8154

Cited by 48 publications

(30 citation statements)

References 35 publications

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“…Particularly, flow-through diffusion cells are widely introduced, with merits in automating sample collection cell and facilitating the maintenance of skin viability by continually pumping and replacing the physiological receptor fluid [44]. As reported by Beckley-Kartey et al [45], testosterone was metabolized in viable human, rat and mouse skin to a range of hydroxylated metabolites during in vitro percutaneous absorption in flowthrough diffusion cells, indicating the presence of CYP activity in skin tissues. On the other hand, using the same diffusion cells, Yourick and Bronaugh [46] observed significant differences in metabolism of 2-nitro-p-phenylenediamine (a hair dye) through human and rat skin.…”

Section: In Vitro Absorption/metabolism Studiesmentioning

confidence: 93%

Cutaneous Metabolism in Transdermal Drug Delivery

Zhang¹,

Grice²,

Wang³

et al. 2009

CDM

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The skin is the major interface between the body and the environment. The cutaneous metabolic activity has been identified and widely studied in recent years. It is clear that active enzymes in viable skin tissues have a capacity for bio-transforming topically applied compounds, with a consequence of an altered pharmacological effect. Although the extent of cutaneous metabolism is modest compared to major metabolism in liver, it is important to consider the effect of inherent metabolic function on both local and systematic transdermal delivery. In this review, recent literatures concerning in vitro & in vivo models and techniques used in the study of skin metabolic processes were summarized. The potential influence from skin transporters, diseased conditions, and the chemicals used in skin absorption studies on cutaneous metabolic function, was then discussed. We also reviewed the prodrug design strategy and its applications in transdermal drug delivery.

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Section: In Vitro Absorption/metabolism Studiesmentioning

confidence: 93%

Cutaneous Metabolism in Transdermal Drug Delivery

Zhang¹,

Grice²,

Wang³

et al. 2009

CDM

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“…Some authors report that expected human skin metabolism of specific xenobiotics is not observed, e.g. for diclofenac [27] and coumarin [28].…”

Section: B) the Use Of Ex Vivo Human Skin In In Vitro Skin Absorptionmentioning

confidence: 97%

Xenobiotic Metabolism in Human Skin and 3D Human Skin Reconstructs: A Review

Gibbs¹,

Sandt²,

Merk³

et al. 2007

CDM

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In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental chemical exposure, it is also a potential target organ for adverse health effects. Occupational, accidental or intended-use exposure to toxic chemicals could result in acute or delayed injury to the skin (e.g. inflammation, allergy, cancer). Skin metabolism may play a role in the manifestation or amelioration of adverse effects via the topical route. Today, we have robust testing strategies to assess the potential for local skin toxicity of chemical exposure. Such methods (e.g. the local lymph node assay for assessing skin sensitisation; skin painting carcinogenicity studies) incorporate skin metabolism implicitly in the in vivo model system used. In light of recent European legislation (i.e. 7(th) Amendment to the Cosmetics Directive and Registration Evaluation and Authorisation of existing Chemicals (REACH)), non-animal approaches will be required to reduce and replace animal experiments for chemical risk assessment. It is expected that new models and approaches will need to account for skin metabolism explicitly, as the mechanisms of adverse effects in the skin are deconvoluted. 3D skin models have been proposed as a tool to use in new in vitro alternative approaches. In order to be able to use 3D skin models in this context, we need to understand their metabolic competency in relation to xenobiotic biotransformation and whether functional activity is representative of that seen in human skin.

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“…Likewise, Yourick and Bronaugh (1997) as well as Beckley-Kartey et al (1997) noticed no cutaneous metabolism of coumarin in the rat and Bronaugh et al (1989) reported lack of cutaneous metabolism for caffeine and DDT. In the minipig skin an important consequence of the virtual lack of cutaneous metabolism of rivastigmin is its high systemic availability upon application to the skin, since this avoids its large first-pass hepatic metabolism (Tse and Laplanche 1998).…”

Section: Introductionmentioning

confidence: 98%

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

2018

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Studies on the metabolic fate of medical drugs, skin care products, cosmetics and other chemicals intentionally or accidently applied to the human skin have become increasingly important in order to ascertain pharmacological effectiveness and to avoid toxicities. The use of freshly excised human skin for experimental investigations meets with ethical and practical limitations. Hence information on xenobiotic-metabolizing enzymes (XME) in the experimental systems available for pertinent studies compared with native human skin has become crucial. This review collects available information of which—taken with great caution because of the still very limited data—the most salient points are: in the skin of all animal species and skin-derived in vitro systems considered in this review cytochrome P450 (CYP)-dependent monooxygenase activities (largely responsible for initiating xenobiotica metabolism in the organ which provides most of the xenobiotica metabolism of the mammalian organism, the liver) are very low to undetectable. Quite likely other oxidative enzymes [e.g. flavin monooxygenase, COX (cooxidation by prostaglandin synthase)] will turn out to be much more important for the oxidative xenobiotic metabolism in the skin. Moreover, conjugating enzyme activities such as glutathione transferases and glucuronosyltransferases are much higher than the oxidative CYP activities. Since these conjugating enzymes are predominantly detoxifying, the skin appears to be predominantly protected against CYP-generated reactive metabolites. The following recommendations for the use of experimental animal species or human skin in vitro models may tentatively be derived from the information available to date: for dermal absorption and for skin irritation esterase activity is of special importance which in pig skin, some human cell lines and reconstructed skin models appears reasonably close to native human skin. With respect to genotoxicity and sensitization reactive-metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the Conclusions section in the end of this review.

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Comparativein VitroSkin Absorption and Metabolism of Coumarin (1,2-Benzopyrone) in Human, Rat, and Mouse

Cited by 48 publications

References 35 publications

Cutaneous Metabolism in Transdermal Drug Delivery

Cutaneous Metabolism in Transdermal Drug Delivery

Xenobiotic Metabolism in Human Skin and 3D Human Skin Reconstructs: A Review

Xenobiotica-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

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