Influence of metabolism in skin on dosimetry after topical exposure.

Bronaugh, Robert L.; Collier, Steven W.; Macpherson, Sara E.; Kraeling, Margaret E. K.

doi:10.1289/ehp.94102s1171

Cited by 26 publications

(9 citation statements)

References 10 publications

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“…The drug molecules or chemical substances may exhibit greater or lesser biological activity that undergoes significant skin metabolism than predicted simply from skin penetration studies. The in vivo measurement of skin metabolism is difficult task because biological specimens may also contain metabolites from other tissues (Bronaugh et al, 1994). However, the skin metabolism can be evaluated by conducting in vitro permeation studies using viable skin or the metabolites can be measured in skin homogenate or in the receptor fluid (Bronaugh, 1995).…”

Section: Skin Metabolismmentioning

confidence: 99%

“…In addition, the presence of enzymes in skin causes variation of the structure of molecules and alters topical bioavailability. Hence, the in vivo activity of dermatological formulation depends on bioavailability of drug within the skin at the site of action (Bronaugh et al, 1994). In this context, researchers in the last few decades have given much emphasis on the assessment of skin kinetics of topical formulation.…”

Section: Introductionmentioning

confidence: 99%

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Basic considerations in the dermatokinetics of topical formulations

Nair

Jacob

Al‐Dhubiab

et al. 2013

Braz. J. Pharm. Sci.

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Assessing the bioavailability of drug molecules at the site of action provides better insight into the efficiency of a dosage form. However, determining drug concentration in the skin layers following topical application of dermatological formulations is a great challenge. The protocols followed in oral formulations could not be applied for topical dosage forms. The regulatory agencies are considering several possible approaches such as tape stripping, microdialysis etc. On the other hand, the skin bioavailability assessment of xenobiotics is equally important for topical formulations in order to evaluate the toxicity. It is always possible that drug molecules applied on the skin surface may transport thorough the skin and reaches systemic circulation. Thus the real time measurement of molecules in the skin layer has become obligatory. In the last two decades, quite a few investigations have been carried out to assess the skin bioavailability and toxicity of topical/dermatological products. This review provides current understanding on the basics of dermatokinetics, drug depot formation, skin metabolism and clearance of drug molecules from the skin layers following application of topical formulations.Uniterms: Dermatological formulations/pharmacokinetics. Dermatological formulations/ toxicity. Dermatokinetics. Skin/metabolism. Microdialysis. Tape stripping.A avaliação da biodisponibilidade de moléculas de fármacos no sítio de ação oferece melhor compreensão sobre a eficiência da forma de dosagem. Entretanto, a determinação da concentração de fármaco nas camadas da pele em seguida à aplicação tópica de formulações dermatológicas é um grande desafio. Os protocolos seguidos para as formulações orais não podem ser aplicados para as formulações tópicas. As agências regulatórias consideram várias abordagens possíveis, tape stripping, microdiálise etc. Por outro lado, a avaliação da biodisponibilidade de xenobióticos na pele é igualmente importante para as formulações tópicas para se avaliar a toxicidade. É sempre possível que as moléculas de fármaco aplicadas na superfície da pele sejam transportadas através da pele e alcancem a circulação sistêmica. Assim, a medida em tempo real de moléculas na camada da pele tem se tornado obrigatória. Nas últimas duas décadas, realizaram-se poucas pesquisas para avaliar a biodisponibilidade da pele e a toxicidade de produtos tópicos/dermatológicos. Esta revisão fornece a compreensão atual com base na dermatocinética, formação de fármaco de depósito, metabolismo da pele e o clearance das moléculas de fármaco das camadas da pele em seguida à aplicação de formulações tópicas.Unitermos: Formulações dermatológicas/farmacocinética. Formulações dermatológicas/toxicidade. Dermatocinética Pele/metabolismo. Microdiálise. Tape stripping.

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Section: Skin Metabolismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Basic considerations in the dermatokinetics of topical formulations

Nair

Jacob

Al‐Dhubiab

et al. 2013

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

show abstract

“…However, the skin is a metabolically active tissue expressing biotransformation enzymes. These enzymes are able to metabolize xenobiotics which are in contact with skin [4]. These metabolic processes can play an important role in the fate of topically applied substances and therefore modulate their systemic bioavailability [5,6].…”

Section: Introductionmentioning

confidence: 99%

Effect of Skin Metabolism on Dermal Delivery of Testosterone: Qualitative Assessment using a New Short-Term Skin Model

Jacques

Perdu

Jamin

et al. 2014

Skin Pharmacol Physiol

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The skin is a metabolically active organ expressing biotransformation enzymes able to metabolize both endogenous molecules and xenobiotics. We investigated the impact of metabolism on the delivery of testosterone through the skin with an ex vivo pig ear skin system as an alternative model for human skin. Penetration, absorption and metabolic capabilities were investigated up to 72 h after application of [¹⁴C]-testosterone doses of 50-800 nmol on either fresh or frozen skin, with the latter model being metabolically inactive. Testosterone absorption and metabolite production were monitored by radio-HPLC and gas chromatography-mass spectrometry. Testosterone absorption through frozen skin was much lower, irrespective of the dose of testosterone applied, compared to fresh skin. Using fresh skin samples, >95% of the radioactivity recovered in culture media, as well as the skin itself, corresponded to metabolites. These results were compared with the metabolic data obtained from other in vitro systems (liver and skin microsomes). The present work leads to the conclusion that most of the enzymatic activities expressed in liver fractions are also expressed in pig and human skin. The metabolic activity of the skin can modulate the biological activity of pharmaceuticals (and xenobiotics). Consequently, it can also greatly affect transdermal drug delivery.

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“…A primary role for the stratum corneum is the presentation of a barrier for loss of water or entry of environmental agents (Beisson et al, 2001). The epidermis has many recognized functions, including generation of the corneocytes forming the stratum corneum, recognition of environmental antigens (Stingl and Steiner, 1989), metabolism of xenobiotics (Bronaugh et al, 1994;Steinstrasser and Merkle, 1995) and production of melanin by epidermal melanocytes to moderate damage by ultraviolet light. Unlike the epidermis, the dermis is heavily vascularized and, thus, is able to play a role in thermoregulation.…”

Section: Introductionmentioning

confidence: 99%

Levels of retinyl palmitate and retinol in stratum corneum, epidermis and dermis of SKH-1 mice

et al. 2006

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Vitamin A (retinol) regulates many biological functions, including epidermal cell growth. Retinyl palmitate (RP) is the major esterified form of retinol and the predominant component of retinoids in the skin; however, how endogenous levels of RP and retinol in the skin are affected by the age of the animal remains unknown. Furthermore, the levels of retinol and RP in the various skin layers - the stratum corneum, epidermis and dermis of skin - have not been reported. In this paper, we report the development of a convenient method for separation of the skin from SKH-1 female mice into the stratum corneum, epidermis, and dermis and the determination of the levels of RP and retinol in the three fractions by HPLC analysis. The total quantities of RP and retinol from the stratum corneum, epidermis, and dermis are comparable to those extracted from the same amount of intact skin from the same mouse. There was an age-related effect on the levels of RP and retinol in the skin and liver of female mice. An age-related effect was also observed in the stratum corneum, epidermis, and dermis. The levels of RP and retinol were highest in the epidermis of 20-week-old mice, and decreased when the age increased to 60- and 68-weeks. The total amount of RP at 20 weeks of age was found to be 1.52 ng/mg skin, and decreased about 4-fold at 60- and 68-weeks of age. A similar trend was found for the effects of age on the levels of retinol.

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Influence of metabolism in skin on dosimetry after topical exposure.

Cited by 26 publications

References 10 publications

Basic considerations in the dermatokinetics of topical formulations

Basic considerations in the dermatokinetics of topical formulations

Effect of Skin Metabolism on Dermal Delivery of Testosterone: Qualitative Assessment using a New Short-Term Skin Model

Levels of retinyl palmitate and retinol in stratum corneum, epidermis and dermis of SKH-1 mice

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