Mechanisms of action of topical therapies and the rationale for combination therapy

Norris, David A.

doi:10.1016/j.jaad.2005.04.027

Cited by 97 publications

(96 citation statements)

References 60 publications

(76 reference statements)

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“…The mechanisms of action of calcineurin inhibitors are different from those of glucocorticoids [13]. Calcineurin inhibitors form complexes with intracellular macrophilin-12, previously known as FK506-binding protein, and calcium-calmodulin and inhibit the activity of calcineurin, which activates nuclear factor of activated T cells (NFAT), leading to repression of the genes activated by NFAT.…”

Section: Discussionmentioning

confidence: 99%

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Glucocorticoids Inhibit Double-Stranded RNA-Induced Thymic Stromal Lymphopoietin Release from Keratinocytes in an Atopic Cytokine Milieu More Effectively than Tacrolimus

Lê¹,

Takai²,

Vu³

et al. 2010

Int Arch Allergy Immunol

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Background: Thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes in skin lesions in atopic dermatitis and bronchial epithelial cells in asthma, plays a key role in allergic diseases. Double-stranded RNA (dsRNA) stimulates keratinocytes to release TSLP in vitro. Objective: To examine the potential of glucocorticoids and calcineurin inhibitors to suppress dsRNA-induced release of TSLP from keratinocytes. Methods: Primary human kerarinocytes were stimulated with dsRNA in the presence of IL-4, IL-13 and TNF-α. TSLP release was measured by ELISA. The effects of glucocorticoids and 2 calcineurin inhibitors, cyclosporin A and FK506/tacrolimus, were analyzed. Results: The glucocorticoids inhibited dsRNA-induced release of TSLP. The inhibitory effect became saturated (50–70% reduction) at concentrations higher than 10^–10M. Cyclosporin A inhibited the release of TSLP by 50–60% at 10^–5 and 10^–4M. FK506 had no effect at 10^–5M or less, but almost completely inhibited the release of TSLP at 10^–4M. No synergistic effect was obtained with a glucocorticoid plus either of the calcineurin inhibitors. An additive inhibitory effect was obtained with a glucocorticoid plus 10^–5M cyclosporin A. Glucocorticoid inhibited dsRNA-induced TSLP transcription in the absence of Th2/TNF cytokines. Conclusions: Glucocorticoids inhibited the dsRNA-induced release of TSLP in the atopic cytokine milieu at much lower concentrations than calcineurin inhibitors, suggesting that they could be effective in the treatment of atopic dermatitis when exogenous or endogenous dsRNA is involved in the pathogenesis. In addition, the in vitro system established in this study would be useful for screening of therapeutic reagents which target TSLP expression.

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Section: Discussionmentioning

confidence: 99%

“…Topical glucocorticoids and calcineurin inhibitors such as FK506/tacrolimus are a mainstay of the treatment of atopic dermatitis [13]. Glucocorticoids suppress the dsRNA-induced release of TSLP in human airway epithelial cells [14].…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoids Inhibit Double-Stranded RNA-Induced Thymic Stromal Lymphopoietin Release from Keratinocytes in an Atopic Cytokine Milieu More Effectively than Tacrolimus

Lê¹,

Takai²,

Vu³

et al. 2010

Int Arch Allergy Immunol

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“…As these agents act through different mechanisms, there is a scientific rationale for their use in combination therapy. The rationale assumes that agents are selected on the basis of their individual mechanisms of action, which may offer the possibility of additive or synergistic efficacy, reduction in the dose of either or both products, and reduction in the occurrence of side effects (Norris 2005). Several studies have proven the advantages of using a combination of topical medications for treatment of psoriasis.…”

Section: Combination Topical Therapiesmentioning

confidence: 99%

Topical Therapies for Psoriasis

Mitra¹,

Atillasoy²

2012

Psoriasis

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“…Stimulation of gastric motility has been proposed to accelerate the healing of gastric ulcer and prokinetic agents such as domperidone are known to enhance gastrointestinal motility and prevent duodenogastric reflux. The aim of combining two or more drugs with complementary modes of action using ion exchange resins is to produce the desired release pattern and therapeutic benefits along with the advantage of reducing the complexity of the dosage regimen thus leading to patient compliance (Norris et al, 2005). In the present study, sustained release of domperidone was achieved by complexing with Indion 244 while the immediate release form of ranitidine hydrochloride was prepared by complexing with Indion 294.…”

Section: Introductionmentioning

confidence: 98%

Novel ion exchange resin-based combination drug-delivery system for treatment of gastro esophageal reflux diseases

Bhalekar¹,

Kadam²,

Patil³

et al. 2010

Braz. J. Pharm. Sci.

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The present study involves preparation and characterization of a combination tablet of ranitidine in immediate release form and domperidone in sustained release form, using ion exchange resins. Ranitidine lowers acid secretion, while domperidone release over a prolonged period improves gastric motility thus justifying this combination in gastro esophageal reflux diseases (GERD) and ensuring patient compliance. Drug loading was carried out by batch method & resinates were characterized using FTIR, XRPD. Resinates were formulated as a combination tablet and evaluated for tablet properties & in vitro drug release. Resinates provided sustained release of domperidone and immediate release of ranitidine. IR and X-ray studies indicate complexation of drug and resin along with monomolecular distribution of drugs in amorphous form in the resin matrix. The tablets of resinate combination showed good tablet properties. In-vitro drug release gave desired release profiles and ex-vivo drug absorption studies carried out by placing everted rat intestine in dissolution medium indicated statistically significant similarity in absorption from test and marketed formulation. The novelty of this study is that the retardation in release of domperidone from resinates is achieved by presence of weak resin in the formulation.Uniterms: Drugs/delivery system. Ranitidine/tablets/immediate release. Domperidone/tablets/sustained release. Tablets/delivery system. Ion exchange resins/use/ drugs delivery system. O presente estudo envolve a preparação e a caracterização de associação do comprimido de ranitidina de liberação imediata e domperidona de liberação prolongada, utilizando resinas de troca iônica. A ranitidina diminui a secreção ácida, enquanto a liberação prolongada de domperidona melhora a motilidade gástica, justificando, dessa forma, a associação em doenças de refluxo gastroesofágico (DRGE) e garantindo a adesão do paciente. A carga de fármaco foi efetuada pelo método em batelada e os resinatos, caracterizados utilizando-se FTIR e XRPD. Os resinatos foram formulados como comprimido da associação e avaliados com relação às propriedades dos comprimidos e liberação do fármaco in vitro. Os resinatos proporcionaram a liberação prolongada da domperidona e a liberação imediata da ranitidina. IV e estudos de difração de raios X indicaram a complexação do fármaco e da resina junto com a distribuição monomolecular dos fármacos, em estado amorfo, na matriz da resina. Os comprimidos da associação do resinato apresentaram boas propriedades. Obtiveram-se os perfis de liberação in vitro e os estudos de absorção dos fármacos ex vivo realizados com intestino de rato em meio de dissolução indicaram semelhança significativa na absorção entre as formulações teste e comercializada. A inovação do trabalho é que o retardamento da liberação da domperidona dos resinatos é atingido pela presença de resina fraca na formulação.

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Mechanisms of action of topical therapies and the rationale for combination therapy

Cited by 97 publications

References 60 publications

Glucocorticoids Inhibit Double-Stranded RNA-Induced Thymic Stromal Lymphopoietin Release from Keratinocytes in an Atopic Cytokine Milieu More Effectively than Tacrolimus

Glucocorticoids Inhibit Double-Stranded RNA-Induced Thymic Stromal Lymphopoietin Release from Keratinocytes in an Atopic Cytokine Milieu More Effectively than Tacrolimus

Topical Therapies for Psoriasis

Novel ion exchange resin-based combination drug-delivery system for treatment of gastro esophageal reflux diseases

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