Application of Dermal Microdialysis for the Determination of Bioavailability of Clobetasol Propionate Applied to the Skin of Human Subjects

Au, Wai Ling; Skinner, M.; Benfeldt, Eva; Verbeeck, Roger K.; Kanfer, Isadore

doi:10.1159/000330489

Cited by 32 publications

(15 citation statements)

References 55 publications

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“…The identification of probe depth as a relevant variable indicated that the overall methodological variation of dOFM is low. Although the influence of probe depth on kinetics has repeatedly been considered in dermal MD studies ( 15 , 18 ), no significant effect has been published yet. Methodological differences or the different distribution of predominantly water soluble compounds which have been investigated in these dermal MD studies could have prevented the identification of any impact of probe depth variations.…”

Section: Discussionmentioning

confidence: 99%

“…One study performed by Au et al . ( 15 ) investigated the feasibility of CP-17 sampling in the skin, but they applied highly concentrated CP-17 in ethanolic solution, because the high lipophilicity of CP-17 ( LogP = 3.49) precluded the use of a commercial formulation for MD sampling. A study on the penetration behavior of a topical lipophilic drug into healthy and psoriatic lesional skin using tape-stripping followed by skin punch biopsy was performed by Rony et al .…”

Section: Introductionmentioning

confidence: 99%

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Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution

et al. 2016

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PurposeTo evaluate the kinetics of topically applied clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercially available low-strength cream using in vivo dermal open-flow microperfusion (dOFM).MethodsTwelve patients received Dermovate® cream (CP-17, 0.05%) on small lesional and non-lesional skin test sites for 14 days, once daily. On day 1 and 14, dOFM samples were continuously taken in the dermis for 24 h post-dose and analyzed by LC-MS/MS. Probe depths were assessed by 50 MHz ultrasound scanning.ResultsMixed-effects modelling identified skin condition, treatment duration and probe-depth as kinetics determining variables. The time- and depth-resolved intradermal data revealed (i) slower penetration of CP-17 into lesional than into non-lesional skin, (ii) normalized (faster) skin penetration after repeated dosing, and (iii) no CP-17 accumulation within the dermis independently of the skin condition.ConclusionsIntradermal investigation of a highly lipophilic drug released from low-strength cream was successfully performed by using dOFM and timely and spatially, i.e., probe-depth dependent, resolved kinetic data were delivered. These data support the assumption that the thickened psoriatic stratum corneum might act as trap compartment which lowers the skin penetration rate for lipophilic topical drugs.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-016-1960-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution

et al. 2016

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“…In particular, miconazole induces a strong phosphorylation of ERK1/2, whose constitutive activation has been correlated with a profound increase in the extent of remyelination after toxin-induced demyelinating injury [53,59]. In addition, clobetasol, an agonist of glucocorticoid receptor widely used to treat different pathological skin conditions [60], can also act through the smoothened (Smo) receptors [61], whose activity is regulated by cholesterol intermediates [57,58]. As reported below, the efficacy of all these drugs in enhancing OL differentiation has been well documented by several publications and, in the case of clemastine, also by two clinical trials on MS patients.…”

Section: Drugs Promoting Remyelination Through a Potential Action On mentioning

confidence: 99%

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

Marangon

Boccazzi

Lecca

et al. 2020

JCM

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Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.Damage to myelin sheath is present in different severe neurological conditions such as multiple sclerosis (MS), brain ischemia, and amyotrophic lateral sclerosis (ALS). Loss of myelin ultimately results in reduction of nerve conduction velocity and in altered transfer of energy metabolites to neurons which contribute to disease [5,6]. Myelin repair, through the activation, recruitment and differentiation of adult oligodendrocyte precursor cells (OPCs), which become new myelin forming OLs [7], is crucial for limiting axon degeneration and progressive disease disability. During the remyelination process, OPCs undergo profound morphological and functional changes and progressively remodel their membrane composition, increasing the biosynthesis of cholesterol and galactosphingolipids, and reducing the relative amount of phospholipids and proteins [4]. An intricate interaction of environmental signals and cell-intrinsic mechanisms triggered by the immune and inflammatory response to injury is known to limit the regenerative potential of OPCs in MS [8,9]. However, the role of modulators of lipid metabolism in OPC-mediated repair is still not completely elucidated. Of note, recent studies suggest that targeting the lipid pathways in OLs may be a good strategy to promote remyelination [10].Furthermore, in MS, remyelination failure is also strictly correlated to an altered extracellular signaling microenvironment that, among others, affects the organization of OL membranes, which causes defects in myelin at the molecular level [11,12]. Although the ECM is ...

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“…This technique allows continuous sampling during topical drug delivery [15, 18,19]. This sensitive tool has been used to assess local bioavailability of topically delivered drugs in humans [20][21][22], including iontophoretically administered compounds [23] (Figure 2).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Trials and tribulations of skin iontophoresis in therapeutics

Roustit

Blaise

Cracowski

2013

Brit J Clinical Pharma

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Iontophoresis is a method of non-invasive transdermal drug delivery based on the transfer of charged molecules using a low-intensity electric current. Both local and systemic administration are possible; however, the skin pharmacokinetics of iontophoretically delivered drugs is complex and difficult to anticipate. The unquestionable theoretical advantages of the technique make it attractive in several potential applications. After a brief review of the factors influencing iontophoresis, we detail the current applications of iontophoresis in therapeutics and the main potential applications under investigation, including systemic and topical drugs and focusing on the treatment of scleroderma-related ulcerations. Finally, we address the issue of safety, which could be a limitation to the routine clinical use of iontophoresis.

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Application of Dermal Microdialysis for the Determination of Bioavailability of Clobetasol Propionate Applied to the Skin of Human Subjects

Cited by 32 publications

References 55 publications

Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution

Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution

Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

Trials and tribulations of skin iontophoresis in therapeutics

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