Impact of Adult Atopic Dermatitis on Topical Drug Penetration: Assessment by Cutaneous Microdialysis and Tape Stripping

Ortiz, Patricia Garcia; Hansen, Steen Honoré; Shah, Vinod P.; Menné, Torkil; Benfeldt, Eva

doi:10.2340/00015555-0562

Cited by 48 publications

(23 citation statements)

References 22 publications

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“…These studies demonstrated increased drug penetration in barrier-disrupted skin as well as the usefulness of the MD methodology for drug penetration studies. Furthermore MD showed a significant 3-fold increased penetration of topically applied metronidazole in skin with atopic dermatitis compared with unaffected skin [103] .…”

Section: Skin Barrier Functionmentioning

confidence: 99%

“…Other recent studies have compared e.g. the penetration of acyclovir and salicylic acid on disrupted skin barriers using DMD and tape stripping [78] , and the penetration of a metronidazole cream formulation (1%) applied to the forearm skin in areas of both irritant dermatitis and nor- mal skin [42,103] . These studies demonstrated increased drug penetration in barrier-disrupted skin as well as the usefulness of the MD methodology for drug penetration studies.…”

Section: Skin Barrier Functionmentioning

confidence: 99%

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Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Holmgaard

Nielsen

Benfeldt

2010

Skin Pharmacol Physiol

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Microdialysis (MD) in the skin is a unique technique for in vivo sampling of topically as well as systemically administered drugs at the site of action, e.g. sampling the unbound tissue concentrations in the dermis and subcutaneous tissue. MD as a research method has undergone significant development, improvement and validation during the last decade and has proved to be a versatile, safe and valuable tool for pharmacokinetic and pharmacodynamic studies. This review gives an overview of the current state and future perspectives of dermal MD sampling. Methodological issues such as choice of instrumentation, calibration and experimental procedures are discussed along with the analytical considerations necessary for successful sampling. Clinical MD studies in the skin are reviewed with emphasis on pharmacokinetic studies of topically applied drugs with or without impairment of skin barrier function by skin disease or barrier perturbation. A comparison between MD and other tissue sampling techniques reveals the advantages and limitations of the method. Subsequently, an in-depth discussion of the application of MD for the evaluation of bioavailability and bioequivalence of topical formulations is concluded by the current regulatory point of view. The future perspective includes further expansion and validation of the use of MD in the experimental and clinical setting as well as in the optimization of the method for regulatory purposes, i.e. the commercialization of bioequivalent, generic drug products.

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Section: Skin Barrier Functionmentioning

confidence: 99%

Section: Skin Barrier Functionmentioning

confidence: 99%

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Holmgaard

Nielsen

Benfeldt

2010

Skin Pharmacol Physiol

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“…Percutaneous absorption in some diseased skin was reported (Chiang et al, 2012). For example, the cutaneous penetration of a metronidazole cream formulation in the atopic dermatitis or irritant dermatitis was significantly improved in comparison with that in uninvolved skin (Ortiz et al, 2008(Ortiz et al, ,2009). However, the percutaneous penetration of ketoconazole in gydrocortisoneinduced rats group was highly decreased than that in control group (Bi-ya et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The percutaneous permeability and absorption of dexamethasone esters in diabetic rats: a preliminary study

Song

Xiong

et al. 2013

Drug Delivery

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To evaluate the influence of diabetes on the permeation of dexamethasone acetate (DA) and dexamethansone sodium phosphate (DSP), the two major dexamethansone esters in clinical practice, when applied percutaneously, histochemical staining was used to determine the skin morphology; improved Franz diffusion cells and microdialysis were used to assess the percutaneous permeation of DA and DSP in normal and diabetic rats. Histopathological examination showed that the epidermal tissue of diabetic rat was much thinner, the epidermal cell layer was less clear and the stratified arrangement of epidemic cell had almost disappeared and progressive atrophy were developed on the subcutaneous fat. In vitro studies showed that the cumulative and the penetrated DSP amount in Group DM were higher. The mean flux value and the mean depositional amount of Group DM were increased significantly compared to those of Group CTL, whereas the amount of DA penetrating was of no difference. Microdialysis indicated that there was no significant difference between Group CTL and Group DM for all the pharmacokinetic parameters of DA. In contrast, the subcutaneous AUC all values and the C max of DSP were significantly increased compared to the control. In conclusion, diabetic rat skin significantly increased the percutaneous permeation of DSP but had no effect on that of DA. It suggests that patients with diabetes should consider the dose of administration when using DA, DSP or other glucocorticoids topically, as different liposolubilities may play some role in the permeability of these compounds via diabetic skin.

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“…A mutation in the filaggrin gene, which is carried by approximately 9% of the European population, is associated with a decrease in natural moisturizing factor of the skin, a key parameter for skin barrier function and a risk factor for the development of dermatitis [41][42][43]. Patients suffering from dermatitis have previously been shown to have impaired skin barrier function in lesional [44] as well as non-lesional skin [45]. The impact of an impaired skin barrier function may be seen in both the occupational setting but also in penetration and/or reaction to transdermally administered medical products, topical formulations as well as cosmetic products.…”

Section: From Experimental Observations To the Real Worldmentioning

confidence: 99%

Percutaneous Penetration ‐ Methodological Considerations

Holmgaard

Benfeldt

Nielsen

2014

Basic Clin Pharma Tox

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Studies on percutaneous penetration are needed to assess the hazards after unintended occupational skin exposures to industrial products as well as the efficacy after intended consumer exposure to topically applied medicinal or cosmetic products. During recent decades, a number of methods have been developed to replace methods involving experimental animals. The results obtained from these methods are decided not only by the chemical or product tested, but to a significant degree also by the experimental set-up and decisions made by the investigator during the planning phase. The present MiniReview discusses some of the existing and well-known experimental in vitro and in vivo methods for studies of percutaneous penetration together with some more recent and promising methods. After this, some considerations and recommendations about advantages and limitations of the different methods and their relevance for the prediction of percutaneous penetration are given. Which method to prefer will depend on the product to be tested and the question asked. Regulatory guidelines exist for studies on percutaneous penetration, but researchers as well as regulatory bodies need to pay specific attention to the vehicles and solvents used in donor and sampling fluids so that it reflects in-use conditions as closely as possible. Based on available experimental data, mathematical models have been developed to aid predictions of skin penetration. The authors question the general use of the present mathematical models in hazard assessment, as they seem to ignore outliers among chemicals as well as the heterogeneity of skin barrier properties and skin conditions within the exposed populations. This MiniReview will discuss some of the existing and wellknown experimental in vitro and in vivo models together with some more recent and promising models and give some considerations and recommendations about advantages and limitations of the various models and their relevance for predictions of percutaneous penetration. An overview of the methodologies discussed can be found in table 1.Dermal exposure may be unintentional after environmental or occupational exposure or intentional after the use of topically applied medication or use of cosmetic products. In all cases, the assessment of the potential for percutaneous penetration or temporary deposition within the skin is an essential element in assessing risk as well as efficacy after dermal exposures.Decades of preventive efforts have decreased the inhalational exposures at work places. At the same time, topically applied pharmaceuticals are being used ever more often. Together, this has increased the relative importance of dermal exposures.Knowledge concerning percutaneous penetration and the potential to reach target sites closes the gap from exposure assessment and hazard identification to risk assessment. If a substance is unable to penetrate the stratum corneum (SC) or affect the skin barrier function in any way, then the need for further assessment of risk becomes less evide...

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Impact of Adult Atopic Dermatitis on Topical Drug Penetration: Assessment by Cutaneous Microdialysis and Tape Stripping

Cited by 48 publications

References 22 publications

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

The percutaneous permeability and absorption of dexamethasone esters in diabetic rats: a preliminary study

Percutaneous Penetration ‐ Methodological Considerations

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