Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus

Billich, Andreas; Aschauer, Heinrich; Aszódi, András; Stuetz, Anton

doi:10.1016/j.ijpharm.2003.07.013

Cited by 171 publications

(153 citation statements)

References 16 publications

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“…20,27,[30][31][32]44 The favorable safety and tolerability profile of 1% pimecrolimus cream demonstrated in published pediatric studies 35,[37][38][39]43,44 is supported by the data summarized in this review. The combined analysis of the results from 4 pharmacokinetic studies conducted with 35 infants with AD indicated that pimecrolimus blood concentrations after topical applications were consistently low, irrespective of the level of disease severity and percentage of TBSA involved.…”

Section: Discussionmentioning

confidence: 70%

“…[21][22][23][24][25] Pimecrolimus cream has demonstrated a much lower potential for percutaneous absorption than TCSs, because of its higher molecular weight and lipophilicity. 26,27 Unlike TCSs, it does not cause skin atrophy and does not affect the hypothalamic-pituitary-adrenal axis. 26,28 Pimecrolimus cream was developed specifically for the treatment of inflammatory skin diseases, such as AD, allergic contact dermatitis, and chronic irritant hand dermatitis.…”

mentioning

confidence: 99%

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Safety and Tolerability of 1% Pimecrolimus Cream Among Infants: Experience With 1133 Patients Treated for Up to 2 Years

et al. 2006

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Pimecrolimus is a calcineurin inhibitor developed for the topical treatment of atopic dermatitis. During the clinical development of 1% pimecrolimus cream, 1133 patients 3 to 23 months of age with mild to severe atopic dermatitis were treated for up to 2 years. The objective of this review is to discuss the safety and tolerability of 1% pimecrolimus cream among infants, on the basis of the combined results from all studies (4 pharmacokinetic studies and 6 clinical trials) conducted among these patients. Pimecrolimus blood concentrations measured for 35 patients were consistently low (Յ1 ng/mL in Ͼ80% of samples), irrespective of the disease severity and extent, and remained low during intermittent treatment for up to 1 year. The level of systemic exposure to pimecrolimus among infants was comparable to that observed for older pediatric patients enrolled in the same studies and treated in the same way with 1% pimecrolimus cream, which indicated that young pediatric patients are not at higher risk of significant percutaneous absorption of topically applied pimecrolimus, despite their large skin surface area/body mass ratio. The 6 clinical trials included a total of 1098 infants, who were treated for periods ranging from 4 weeks to 2 years. Most of these patients (60%) had moderate to severe disease at baseline. The most frequently reported adverse events were common childhood disorders such as nasopharyngitis, pyrexia, upper respiratory tract infections, ear infections, and bronchitis. During the double-blind (DB) studies or DB phases of studies, the incidence rates for the most frequently reported adverse events were similar for patients who received 1% pimecrolimus cream and patients who received the vehicle, except for the incidence of teething, which was higher among the pimecrolimus-treated infants (relative risk: 2.02; 95% confidence interval: 1.32-3.27). Treatment with 1% pimecrolimus cream was not associated with an increase in the overall incidence of nonskin infections, compared with the vehicle (relative risk: 1.015; 95% confidence interval: 0.88 -1.18). The incidence density (ID) rates for total bacterial, fungal, parasitic, and viral skin infections during the DB studies or DB phases of www.pediatrics.org/cgi

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Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 99%

Safety and Tolerability of 1% Pimecrolimus Cream Among Infants: Experience With 1133 Patients Treated for Up to 2 Years

et al. 2006

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“…In the permeation experiments, two parameters were obtained: (1) the rate of permeation (flux) of the drug through the skin into the receptor fluid; and (2) the concentration of the drug in the skin (SC+epidermis and dermis). 34 Permeation rates were calculated by taking samples from the receptor phase at various time points, while the skin concentration reported here refers to the 6-hour time point at the end of the experiment.…”

Section: Skin Permeation Experimentsmentioning

confidence: 99%

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

Özcan¹,

Azizoğlu²,

Şenyiğit³

et al. 2013

IJN

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Abstract:The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

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“…9 The structure of pimecrolimus has higher lipophilicity than that of tacrolimus and binds to macrophilin 12 with high affinity. 10 This complex inhibits calcineurin resulting in the suppression of pro-inflammatory cytokine 1 secretion by activated T-cells, specifically that of interferon-, IL-1, IL-2, IL-3, IL-4, IL-5, GM-CSF, and TNF- 11,12 which are believed to be responsible for the damage to melanocytes that results in vitiligo. In vitro research on the effect of calcineurin inhibitors on melanocytes affected by vitiligo may further support the hypothesis that the pathogenesis of vitiligo involves an auto-immune response as well as autocytotoxic components.…”

Section: Pimecrolimusmentioning

confidence: 99%

Topical Calcineurin Inhibitors in the Treatment of Vitiligo

Caridi¹,

Sohn²,

Patel³

2011

Vitiligo - Management and Therapy

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Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus

Cited by 171 publications

References 16 publications

Safety and Tolerability of 1% Pimecrolimus Cream Among Infants: Experience With 1133 Patients Treated for Up to 2 Years

Safety and Tolerability of 1% Pimecrolimus Cream Among Infants: Experience With 1133 Patients Treated for Up to 2 Years

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

Topical Calcineurin Inhibitors in the Treatment of Vitiligo

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