Measurement of the Lymphatic Clearance of the Human Skin Using a Fluorescent Tracer

Leu, Anders J.; Husmann, Marc; Held, Torsten; Frisullo, Roberto; Hoffmann, Ulrich; Uk, Franzeck

doi:10.1159/000051075

Cited by 10 publications

(5 citation statements)

References 17 publications

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“…The extent of the contribution to the dispersion parameter from the lymphatic transport can be gained by simple analysis of data for the transport and clearance of isothiocyanate-dextran (MW=150 kDa) in human skin (24). Figure 2 in this work shows, as a consequence of lymphatic dispersion, isothiocyanatedextran spreads radially in the dermis a distance Δd≈ 0.3 cm (as approximated from the figure) after t=24 h following intra-dermal injection.…”

Section: Discussionmentioning

confidence: 83%

Modelling Dermal Drug Distribution After Topical Application in Human

Anissimov

Roberts

2011

Pharm Res

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Section: Discussionmentioning

confidence: 83%

Modelling Dermal Drug Distribution After Topical Application in Human

Anissimov

Roberts

2011

Pharm Res

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“…Several routes have been classified in the capillary wall structure as pathways available for exchange. Depending on the solutes size, nature and lipophilicity, they may prefer one or more of these pathways (Leu, 2001). Interendothelial cell junctions are the preferred pathway for the transport of hydrophilic solutes and also important for the small lipophilic solutes.…”

Section: Skin Drug Clearancementioning

confidence: 99%

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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“…Leu et al (46) reported on measurement of lymphatic clearance of the human skin of the foot in 20 subjects. 0.01 ml of FITC–dextran was injected intradermally.…”

Section: Human Safety and Adverse Effects After Various Intradermal Umentioning

confidence: 99%

Safety of sodium fluorescein for in vivo study of skin

O’goshi

Serup

2006

Skin Research and Technology

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Background/purpose: Epicutaneous labeling or intradermal injection of the fluorescent sodium fluorescein is being used increasingly to investigate skin conditions in vivo when using non‐invasive devices such as confocal scanning laser microscopy. Sodium fluorescein was used intravenously for decades for the examination of the vasculature of the ocular fundus (fluorescein angiography) and as eye drops for diagnosis of corneal erosions. The objective of this article is to systematically review the literature on fluorescein and conclude its safety in cutaneous research to support research planning and evaluations by ethics committees. Methods: A number of databases and the literature about safety and toxicity of fluorescein in animal and human studies were searched and analyzed. Results: Side effects or adverse events reported in the literature were related to intravenous bolus injection. Transient nausea and vomiting may occur. Other adverse events such as vasovagal reaction, cardiac or respiratory effects and anaphylaxes are extremely rare but may be fatal. Intradermal injection may cause mild itch or pain; systemic adverse event was reported. Epicutaneous labeling is associated with no reported problem. A typical local dose is several magnitudes of order smaller than a typical intravenous dose. Conclusion: Fluorescein has been used for many years in medicine for diagnostic purposes and is widely safe, albeit intravenous bolus injection may cause serious adverse reactions. In the literature, we could not trace reports of local or systemic side effects of topical sodium fluorescein except itch and pain on intradermal injection, however, dependent on the fluorescein preparation used. Local dermal application of fluorescein for in vivo study of skin may be considered widely safe.

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Measurement of the Lymphatic Clearance of the Human Skin Using a Fluorescent Tracer

Cited by 10 publications

References 17 publications

Modelling Dermal Drug Distribution After Topical Application in Human

Modelling Dermal Drug Distribution After Topical Application in Human

Basic considerations in the dermatokinetics of topical formulations

Safety of sodium fluorescein for in vivo study of skin

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