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1.
Int J Mol Sci ; 24(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37894801

RESUMO

The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data. One significant research gap that this article addresses is the need for more efficient and accurate methods for calibrating PBPK models for dermal drug delivery. This manuscript presents a novel approach and an integrated dermal drug delivery model to address this gap that leverages virtual in vitro release (IVRT) and permeation (IVPT) testing data to optimize mechanistic models. The proposed approach was demonstrated through a study involving Desoximetasone cream and ointment formulations, where the release kinetics and permeation profiles of Desoximetasone were determined experimentally, and a computational model was created to simulate the results. The experimental studies showed that, even though the cumulative permeation of Desoximetasone at the end of the permeation study was comparable, there was a significant difference seen in the lag time in the permeation of Desoximetasone between the cream and ointment. Additionally, there was a significant difference seen in the amount of Desoximetasone permeated through human cadaver skin at early time points when the cream and ointment were compared. The computational model was optimized and validated, suggesting that this approach has the potential to bridge the existing research gap by improving the accuracy and efficiency of drug development processes. The model results show a good fit between the experimental data and model predictions. During the model optimization process, it became evident that there was variability in both the permeability and the partition coefficient within the stratum corneum. This variability had a significant and noteworthy influence on the overall performance of the model, especially when it came to its capacity to differentiate between cream and ointment formulations. Leveraging virtual models significantly aids the comprehension of drug release and permeation, mitigating the demanding data requirements. The use of virtual IVRT and IVPT data can accelerate the calibration of PBPK models, streamline the selection of the appropriate doses, and optimize drug delivery. Moreover, this novel approach could potentially reduce the time and resources involved in drug development, thus making it more cost-effective and efficient.


Assuntos
Desoximetasona , Pele , Humanos , Pomadas/farmacologia , Pele/metabolismo , Absorção Cutânea , Simulação por Computador , Administração Cutânea
2.
Int J Mol Sci ; 22(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546426

RESUMO

Psoriasis is a chronic autoimmune skin disease impacting the population globally. Pharmaceutical products developed to combat this condition commonly used in clinical settings are IV bolus or oral drug delivery routes. There are some major challenges for effectively developing new dosage forms for topical use: API physicochemical nature, the severity of the disease state, and low bioavailability present challenges for pharmaceutical product developers. For non-severe cases of psoriasis, topical drug delivery systems may be preferred or used in conjunction with oral or parenteral therapy to address local symptoms. Elastic vesicular systems, termed "niosomes", are promising drug delivery vehicles developed to achieve improved drug delivery into biological membranes. This study aimed to effectively incorporate a corticosteroid into the niosomes for improving the drug bioavailability of desoximetasone, used to treat skin conditions via topical delivery. Niosomes characterization measurements were drug content, pH, spreadability, specific gravity, content uniformity, rheology, and physicochemical properties. Formulations used a topical gelling agent, Carbomer 980 to test for in vitro skin permeation testing (IVPT) and accelerated stability studies. The developed niosomal test gel provided approximately 93.03 ± 0.23% to 101.84 ± 0.11% drug content with yield stresses ranging from 16.12 to 225.54 Pa. The permeated amount of desoximetasone from the niosomal gel after 24 h was 9.75 ± 0.44 µg/cm2 compared to 24.22 ± 4.29 µg/cm2 released from the reference gel tested. Furthermore, a drug retention study compared the test gel to a reference gel, demonstrating that the skin retained 30.88 ng/mg of desoximetasone while the reference product retained 26.01 ng/mg. A controlled drug release profile was obtained with a niosomal formulation containing desoximetasone for use in a topical gel formulation showing promise for potential use to treat skin diseases like psoriasis.


Assuntos
Desoximetasona/administração & dosagem , Portadores de Fármacos/química , Géis/química , Nanoestruturas/química , Tensoativos/química , Administração Cutânea , Administração Tópica , Fenômenos Químicos , Química Farmacêutica , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Permeabilidade , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea , Viscosidade
3.
J Dermatolog Treat ; 32(1): 41-44, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31132897

RESUMO

Objectives: To determine if resistance to topical treatments can be overcome under conditions promoting adherence.Materials and Methods: Twelve psoriasis patients treated with topical 0.25% desoximetasone spray were randomized to either twice daily phone call reminders or no phone call and were treated for 2 weeks. Pruritus Visual Analog Scale (VAS), Psoriasis Area and Severity Index (PASI), Total Lesion Severity Score (TLSS), and, Investigator Global Assessment (IGA) assessed disease severity.Results: Most subjects improved in most scoring parameters. 100%, 91.7%, 83.3%, and 58.3% had improvements in itching, PASI, TLSS, and IGA, respectively.Conclusions: While our sample size was small and treatment duration short, the effect size of topical treatment was large under conditions designed to promote adherence.


Assuntos
Desoximetasona/uso terapêutico , Glucocorticoides/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Desoximetasona/efeitos adversos , Esquema de Medicação , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Cutis ; 105(2): 89-91;E2;E3, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32186523

RESUMO

Most patients with psoriasis have limited disease that should be manageable with topical treatment. However, psoriasis often is resistant to topical treatment. The aim of our study was to determine if patients using psoriasis-resistant topical treatments can be effectively treated with topicals under conditions promoting adherence. During this open-label, randomized, single-center clinical study, 12 patients with moderate psoriasis that previously failed topical treatment were selected and treated with desoximetasone spray 0.25% for 2 weeks. Six patients were randomized to receive twice-daily telephone call reminders to further encourage good adherence. Disease severity was assessed by the visual analog scale for pruritus, psoriasis area and severity index (PASI), total lesion severity score (TLSS), and investigator global assessment (IGA). At the end of the study, most patients improved in most scores. Therefore, apparent resistance to topical treatment often is due to poor adherence and can be overcome, at least over the short term.


Assuntos
Anti-Inflamatórios/administração & dosagem , Desoximetasona/administração & dosagem , Adesão à Medicação , Psoríase/tratamento farmacológico , Administração Cutânea , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Escala Visual Analógica
6.
J Dermatolog Treat ; 31(2): 147-151, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29770722

RESUMO

Introduction: Topical corticosteroids, available in an array of vehicles are used to control a variety of inflammatory skin diseases. Patients preferences for different vehicles may affect their willingness to use treatment. We assess corticosteroid vehicle preference and potential impact of topical characteristics on adherence and quality of life in patients with psoriasis.Methods: Subjects with psoriasis were recruited from Wake Forest University Dermatology Clinic. Subjects sampled desoximetasone 0.25% spray, betamethasone valerate 0.1% cream, triamcinolone acetonide 0.1% ointment, fluocinonide 0.05% gel, betamethasone valerate 0.1% lotion, clobetasol propionate 0.05% foam, and fluocinonide 0.05% solution in a predetermined randomized order. Subjects completed a Vehicle Preference Measure, Determinants of Adherence Measure, and a Determinants of Quality of Life Measure.Results: Patients preferences for the various products were highly variable. Regarding Determinants of Adherence, patients perception of absorption of the medication was ranked as 'quite important/extremely important' by 85% of total subjects. A majority of patients rated medication side effects as 'quite important/extremely important' when asked to consider topical characteristics effect on quality of life.Discussion: There was wide variation in patient preference for topical medication vehicles used for treating psoriasis. Several vehicle characteristics were considered important to adherence. Given the marked variation in vehicle preference, topical treatment should be individualized according to patients preferences.


Assuntos
Glucocorticoides/uso terapêutico , Veículos Farmacêuticos/química , Psoríase/tratamento farmacológico , Administração Tópica , Valerato de Betametasona/efeitos adversos , Valerato de Betametasona/química , Valerato de Betametasona/uso terapêutico , Clobetasol/efeitos adversos , Clobetasol/química , Clobetasol/uso terapêutico , Desoximetasona/efeitos adversos , Desoximetasona/química , Desoximetasona/uso terapêutico , Composição de Medicamentos , Feminino , Fluocinonida/efeitos adversos , Fluocinonida/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/química , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/psicologia , Psoríase/patologia , Qualidade de Vida
7.
Dermatol Ther ; 32(4): e12956, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31070845

RESUMO

Topical potent corticosteroids are the mainstay of treatment for chronic hand eczema (CHE). However, there are numerous adverse effects associated with the chronic use of topical corticosteroids. Calcipotriol has been widely used in psoriasis and has been reported to achieve beneficial effects in several inflammatory diseases. This study aimed to evaluate the efficacy and safety of calcipotriol ointment compared to desoximetasone ointment in the treatment of CHE. Patch testing was performed in all recruited subjects. Then, each hand of the patient was randomly allocated for the application of either calcipotriol ointment or desoximetasone ointment twice daily for 8 weeks. Recurrence was assessed 4 weeks after discontinuation of the treatment. The Hand eczema severity index (HECSI) scores, quartile grading assessments and digital photographs were evaluated. Adverse reactions were also monitored. A total of 13 participants completed the protocol. Mean HECSI scores revealed up to a 75% reduction in both treatments (p < .001) without significant differences between the groups (p > .05). Approximately 70% of the subjects reported more than 75% improvement with calcipotriol at the end of the treatment. Mild scaling and mild dryness were the most common reactions found with calcipotriol and desoximetasone, respectively. In conclusion, calcipotriol ointment is safe and as effective as desoximetasone ointment. Calcipotriol ointment may be an alternative treatment option for CHE.


Assuntos
Calcitriol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Desoximetasona/administração & dosagem , Eczema/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Doença Crônica , Fármacos Dermatológicos/efeitos adversos , Desoximetasona/efeitos adversos , Método Duplo-Cego , Eczema/patologia , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Dermatoses da Mão/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Estudos Prospectivos , Resultado do Tratamento
8.
J Cutan Med Surg ; 23(2): 157-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30556414

RESUMO

PURPOSE:: Topical corticosteroids (TS) are a treatment for atopic dermatitis (AD) and psoriasis (Ps). We assessed whether use of a TS under conditions designed to enhance adherence would be effective in patients who "failed" TS in the outpatient setting. METHODS:: Individuals with treatment-resistant Ps or AD were recruited (AD, n = 12; Ps, n = 12). Six participants were randomized to each of 2 groups of desoximetasone 0.25% spray alone (n = 6) or desoximetasone spray plus twice-daily phone call reminders to use the medication. Disease severity was assessed. RESULTS:: In treatment-resistant Ps patients, desoximetasone spray, with reminders, resulted in statistically significant improvement in all outcome measures. In treatment-resistant AD patients, there was statistically significant improvement in some assessments. Despite the very small sample size and short evaluation time, statistically significant changes were detected in this cohort. This is evidence of the large effect size of TS for Ps and AD when the treatment is used. CONCLUSIONS:: Patients with "treatment-resistant" Ps and AD generally responded well to the use of desoximetasone spray in the trial setting. This may be due to better adherence in the study environment or patients' preference for the spray vehicle. Patient reminders contributed to improved clinical outcomes in Ps and AD patients with "treatment-resistant" disease.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Desoximetasona/administração & dosagem , Psoríase/tratamento farmacológico , Sistemas de Alerta , Administração Cutânea , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Desoximetasona/uso terapêutico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Telefone , Adulto Jovem
9.
J Dermatolog Treat ; 29(3): 269-271, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29098900

RESUMO

PURPOSE: Desoximetasone 0.25% topical spray is a novel formulation that has not been tested or approved for safety and efficacy. The primary objective was to determine the potential of desoximetasone 0.25 and 0.05% topical sprays, as well as a vehicle to induce photoallergic skin reaction after repeated topical application and irradiation to the skin using a controlled photopatch testing procedure. MATERIALS AND METHODS: 53 subjects completed the study, each with six application sites (two of each treatment), three of which were irradiated and three non-irradiated, for an induction period of three weeks and then challenge period at week 6. RESULTS: Desoximetasone 0.25 and 0.05%, as well as vehicle showed no evidence of potential to induce photosensitization. There was statistically significantly greater irritation at the vehicle irradiated site in comparison to the irradiated treatment area of desoximetasone 0.25% (p = .005) and the irradiated treatment area of desoximetasone 0.05% (p = .008). CONCLUSION: Our results suggest that regular treatment with desoximetasone 0.25 and 0.05% spray, followed by UV light exposure does not induce photosensitization or photo-irritation. These findings increase confidence for the use of this topical spray in eczema or psoriasis patients who may also be receiving UV light therapy and may contribute to the clinical management of these patients.


Assuntos
Desoximetasona/farmacologia , Pele/efeitos dos fármacos , Administração Tópica , Adolescente , Adulto , Idoso , Desoximetasona/efeitos adversos , Esquema de Medicação , Composição de Medicamentos , Feminino , Gastroenteropatias/etiologia , Humanos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Pele/efeitos da radiação , Resultado do Tratamento , Raios Ultravioleta , Adulto Jovem
10.
J Dermatolog Treat ; 29(4): 415-417, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29098908

RESUMO

PURPOSE: The safety and potential side effects of desoximetasone 0.25% and 0.05% sprays have not previously been studied. The primary objective of this study was to determine the irritation potential of desoximetasone 0.25%, 0.05% and vehicle sprays in response to irradiation. MATERIALS AND METHODS: Thirty-four subjects were enrolled in the study, each with three study treatments (desoximetasone 0.25%, 0.05% topical sprays and vehicle) were applied to two sites each on the back of every subject, with half of the sites irradiated with filtered UV light. Dermal reactions at the test sites were evaluated using a visual scale with corresponding numerical scores that rated the degree of erythema and oedema. RESULTS: Desoximetasone 0.25%, 0.05%, and vehicle caused no detectable signs of phototoxicity when examined on days 3 and 4. Mean scores of desoximetasone 0.25%, 0.05% and vehicle to non-irradiated treatment areas showed no signs of irritation. CONCLUSIONS: Our results suggest that regular application of desoximetasone 0.25% and 0.05% topical sprays do not induce photosensitization or photoirritation. The safety of this topical spray may help with clinical management of patients using topical corticosteroids while also receiving therapeutic UV light exposure. Thus, patients can use desoximetasone sprays without concerns of side effects due to therapeutic light or sun exposure.


Assuntos
Fármacos Dermatológicos/farmacologia , Desoximetasona/farmacologia , Pele/efeitos dos fármacos , Administração Tópica , Adulto , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/química , Desoximetasona/efeitos adversos , Desoximetasona/química , Método Duplo-Cego , Eritema/patologia , Eritema/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/efeitos da radiação , Raios Ultravioleta , Adulto Jovem
11.
J Dermatolog Treat ; 29(1): 32-35, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28504031

RESUMO

BACKGROUND: Traditionally, ointments were the vehicle of choice for psoriasis. Poor adherence of traditional vehicles limits the use of topical corticosteroids. Alternative formulations have gained popularity due to their ease of application, improved adherence and efficacy. OBJECTIVE: To evaluate the efficacy of topical desoximetasone 0.25% spray formulation in extensive psoriasis. METHODS: This multicenter, double-blinded, randomized trial compared twice daily topical 0.25% desoximetasone spray to placebo in subjects ≥18 with moderate to severe plaque psoriasis. Primary outcome of the study was the proportion of subjects in each group that achieved clinical success (Physician Global Assessment [PGA] of 0 or 1) and/or treatment success at (target lesion score of 0 or 1) day 28. RESULTS: One-hundred-and-twenty subjects were enrolled. At baseline, 75.0% and 73.3% of the treatment and placebo group had at least moderate PGA, respectively. Clinical success in the intended-to treat and placebo group was 30% and 5% (p = .0003), respectively; treatment success was 39% and 7% (p < .0001), respectively. LIMITATIONS: The lack of standardized outcomes for topical psoriasis treatments limits the ability to compare the results to other treatments. CONCLUSIONS: Topical desoximetasone spray provides rapid control of moderate to severe psoriasis lesions and may be considered for patients awaiting approval of biologicals. TRIAL REGISTRATION: Clinical Trial was registered at clinicaltrial.gov: NCT01206387.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Desoximetasona/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Psoríase/patologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
12.
J Dermatolog Treat ; 29(1): 36-38, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28494626

RESUMO

BACKGROUND: In extensive psoriasis, topical corticosteroids are generally only used to supplement phototherapy and systemic therapy. Spray formulations are easier than other vehicle preparations to apply and may be an option for treating extensive psoriasis. OBJECTIVE: To evaluate the potential for hypothalamic-pituitary-adrenal axis suppression and efficacy of topical desoximetasone 0.25% spray formulation in patients with extensive psoriasis. METHODS: A multicenter, open label, nonrandomized, clinical trial was conducted. Two groups of 12 adults with moderate to severe plaque-type psoriasis were treated with 0.25% desoximetasone spray for 28 days. Physician global assessment (PGA) and body surface area (BSA) were assessed. Cortisol-induced suppression test was performed at baseline, day 14 and day 28 to assess safety. RESULTS: No statistically significant difference was seen in adrenal suppression; odds ratio of 0.779 (p = .85). The mean PGA improvement from baseline was 1.83 and 1.33 for moderate and severe psoriasis, respectively. Mean BSA involvement at baseline for moderate and severe psoriasis was 11% and 23%, respectively, improving to 5% and 19%, respectively. CONCLUSIONS: Considerable improvement can be achieved with short-term potent topical corticosteroid treatment even in patients with severe, extensive psoriasis. For such use, topical desoximetasone has less risk of HPA-suppression than does topical clobetasol.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Desoximetasona/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Superfície Corporal , Composição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sistema Hipófise-Suprarrenal , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
13.
J Drugs Dermatol ; 16(10): 972-975, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29036250

RESUMO

BACKGROUND: Topical corticosteroids offer great efficacy in controlling a wide variety of dermatoses. Traditional ointment vehicles are messy and difficult to apply, which might limit adherence. Alternative vehicle formulations such as topical sprays might improve adherence due to their ease of application. The potency of desoximetasone spray is not fully characterized. OBJECTIVE: To evaluate the relative vasoconstrictive potency of desoximetasone 0.25% topical spray formulation. METHODS: This is a randomized, blinded, single-center study comparing the vasoconstrictive properties of desoximetasone 0.25% topical spray to placebo and seven other known potency topical corticosteroid formulations. The primary endpoint was the degree of vasoconstriction measured using a colorimeter device. RESULTS: Thirty-two healthy subjects met eligibility criteria. Desoximetasone 0.25% topical spray (REGWQ Grouping = A) showed a trend toward greater vasoconstrictive potency compared to clobetasol propionate 0.05% spray (REGWQ Grouping = A). No adverse or serious events were reported. LIMITATIONS: The trial enrolled 90% females, which may affect the external validity of the study. Different populations may respond differently to desoximetasone spray. CONCLUSIONS: Desoximetasone 0.25% topical spray is a high to super high range of potency (Class I to Class II) steroid formulation. Given the cosmetic acceptability of spray products, we anticipate that this type of product would be highly effective for the treatment of inflammatory diseases in clinical practice.

J Drugs Dermatol. 2017;16(10):972-975.

.


Assuntos
Clobetasol/farmacologia , Desoximetasona/farmacologia , Glucocorticoides/farmacologia , Vasoconstrição/efeitos dos fármacos , Administração Cutânea , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Desoximetasona/administração & dosagem , Método Duplo-Cego , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Vasoconstritores/administração & dosagem , Vasoconstritores/farmacologia , Adulto Jovem
14.
J Drugs Dermatol ; 16(9): 919-922, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28915287

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disorder. One of the most disturbing symptoms of AD is pruritus. The first line treatment for AD is topical corticosteroids, topical immunomodulators, topical barrier creams, oral antihistamines, and systemic treatments. Desoximetasone 0.25% spray is a superpotent topical corticosteroid delivered in a novel way and it may be a suitable option for the treatment of pruritus in adult atopic dermatitis patients. STUDY DESIGN: A single-center, open labeled pilot study was conducted to investigate the efficacy and safety of desoximetasone 0.25% spray for pruritus in adult atopic dermatitis patients. RESULTS: Twice daily application of desoximetasone 0.25% spray to affected areas resulted in a significant reduction in all outcomes (IGA, pruritus, VAS assessment of pruritus) within 1 week of initiation of treatment. The reductions exhibited were sustained throughout the study period of 4 weeks. Significant improvements in quality of life, as measured by the DLQI, were observed. No adverse events were reported. CONCLUSION: Desoximetasone 0.25% spray is effective for treating pruritic symptoms of AD. Given its efficacy and convenience as a spray, desoximetasone 0.25% spray should continue to be evaluated as a treatment for AD in larger trials.

J Drugs Dermatol. 2017;16(9):919-922.

.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Desoximetasona/administração & dosagem , Prurido/tratamento farmacológico , Administração Cutânea , Adulto , Dermatite Atópica/patologia , Fármacos Dermatológicos/efeitos adversos , Desoximetasona/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prurido/etiologia , Qualidade de Vida , Resultado do Tratamento
15.
J Drugs Dermatol ; 16(8): 755-758, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28809990

RESUMO

BACKGROUND: Topical corticosteroids are the most common dermatologic medications and are available in numerous different vehicles. Adherence is limited by traditional vehicles because they are messy and time consuming to apply. The preferred spray formulations have the advantage of being applied with ease, resulting in improved adherence and subsequently improved psoriasis. One limitation of topical treatments, especially spray vehicles, is the potential for irritation and sensitization.

OBJECTIVE: To evaluate the irritation and sensitization potential of topical desoximetasone spray formulation.

METHODS: A multicenter, double-blinded, randomized, controlled study assessed the irritancy and sensitization of 0.25% and 0.05% topical desoximetasone spray. Controls included vehicle, a positive control (0.1% sodium lauryl sulfate), negative control (0.9% saline), and an active comparator control (clobetasol spray). The primary outcome of the study was to evaluate the difference in mean cumulative irritation and potential sensitization response of desoximetasone 0.25% and 0.05% topical sprays.

RESULTS: Of the 297 enrolled, 269 completed the study per protocol for the irritation phase and 250 completed the protocol for the sensitization phase. At 22 days, desoximetasone 0.25 and 0.5% spray were less irritating than clobetasol 0.05% spray; mean irritation score difference of -0.46 and -0.57, respectively. Median total irritation score over the 22 days was 0 for all products. No subjects demonstrated any sensitization reaction to any of the six products. No serious adverse reactions were reported.

LIMITATIONS: Selection bias, use of a healthy population, limits the external validity. In addition, the duration of the study was short lived, unlike numerous inflammatory skin diseases. CONCLUSIONS: Desoximetasone spray has little potential for irritation or sensitization. The availability of another spray option for patients desiring less messy treatment may facilitate better adherence and treatment outcomes.

J Drugs Dermatol. 2017;16(8):755-758.

.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Desoximetasona/administração & dosagem , Administração Cutânea , Adolescente , Adulto , Idoso , Fármacos Dermatológicos/efeitos adversos , Desoximetasona/efeitos adversos , Método Duplo-Cego , Composição de Medicamentos , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , North Carolina , Veículos Farmacêuticos/administração & dosagem , Veículos Farmacêuticos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
16.
J Drugs Dermatol ; 14(8): 835-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26267727

RESUMO

Data from two Phase 3, double-blind, randomized, vehicle-controlled parallel studies were evaluated to determine the efficacy and safety of twice daily desoximetasone 0.25% spray for the treatment of plaque psoriasis. In addition to global disease assessments, scaling assessments were performed at baseline and at weeks 1, 2, and 4. To qualify for inclusion, subjects were required to have a clinical diagnosis of stable plaque psoriasis involving ≥10% of the body surface area (BSA), a combined target lesion severity score (TLSS) of ≥7 for the target lesion, a plaque elevation score of ≥3 (moderate) for the target lesion, and a Physician Global Assessment (PGA) score of 3 (moderate) or 4 (severe) at baseline for the overall disease severity. At the baseline visit, the mean proportions of BSA affected by psoriasis were 17% (range 10% to 86%) in the desoximetasone 0.25% spray group and 16% (range 10% to 70%) in the vehicle spray group. Approximately 90% of the patients in each group had moderate to very severe scaling at baseline. Desoximetasone 0.25% spray was effective with significant improvements in overall severity and was well tolerated, with dryness, irritation, and pruritus at the application site being the only reported adverse events occurring in >1% of patients, each of which occurred in less than 3% of patients. As a large proportion of psoriasis patients (94%) have reported being bothered by scaling, the relief of scaling was examined in these studies. At week 1, 69.7% of patients on desoximetasone 0.25% spray had scaling that was considered clear / almost clear / mild compared with 48.3% for those on vehicle spray ( P = .0027). By week 4, the proportion of patients with clear / almost clear / mild scaling had risen to 83.9% in the desoximetasone 0.25% spray group (P < .0001). After four weeks of treatment, 66.4% of patients in the topical corticosteroid group had an overall improvement of at least two grades of disease severity. This demonstrates that desoximetasone 0.25% spray provided fast and effective relief of scaling in patients with plaque psoriasis affecting 10% to 86% of their BSA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Desoximetasona/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Superfície Corporal , Desoximetasona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
18.
Mol Carcinog ; 53(6): 488-97, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23852815

RESUMO

Glucocorticoids (GCs) are very effective at preventing carcinogen- and tumor promoter-induced skin inflammation, hyperplasia, and mouse skin tumor formation. The effects of GCs are mediated by a well-known transcription factor, the glucocorticoid receptor (GR). GR acts via two different mechanisms: transcriptional regulation that requires DNA-binding (transactivation) and DNA binding-independent protein-protein interactions between GR and other transcription factors, such as nuclear factor kappa B (NF-κB) or activator protein 1 (AP-1; transrepression). We hypothesize that the transrepression activities of the GR are sufficient to suppress skin tumor promotion. We obtained two GCs (RU24858 and RU24782) that have dissociated downstream effects and induce only transrepression activities of the GR in a number of systems. These compounds bind the GR with high affinity and repress AP-1 and NF-κB activities while showing a lack of GR transactivation. RU24858, RU24782, or control full GCs desoximetasone (DES) and fluocinolone acetonide (FA) were applied to the dorsal skin of SENCAR mice prior to application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), two times per week for 2 weeks. DES, FA and RU24858 reversed TPA-induced epidermal hyperplasia and proliferation, while RU24782 treatment had no effect on these markers of skin tumor promotion. All tested compounds decreased TPA-induced c-jun mRNA levels in skin. DES, FA, and RU24858, but not RU24782, were also able to reverse TPA-induced increases in the mRNA levels of COX-2 and iNOS. These findings show that RU24858 but not RU24782 reduced TPA-induced epidermal hyperplasia, proliferation, and inflammation, while both compounds reversed c-jun mRNA increases in the skin.


Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Desoximetasona/análogos & derivados , Glucocorticoides/farmacologia , Neoplasias Cutâneas/metabolismo , Animais , Animais não Endogâmicos , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Desoximetasona/química , Desoximetasona/farmacologia , Epiderme/efeitos dos fármacos , Epiderme/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/química , Hiperplasia , Interleucina-6/genética , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Proteínas Proto-Oncogênicas c-jun/genética , RNA Mensageiro , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Acetato de Tetradecanoilforbol/efeitos adversos
19.
J Drugs Dermatol ; 12(12): 1404-10, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24301242

RESUMO

Two Phase 3, double-blind, randomized, vehicle-controlled parallel studies evaluated the efficacy and safety of desoximetasone spray 0.25%, a super-potent topical corticosteroid, twice daily vs vehicle spray twice daily for 28 days in adult patients with moderate to severe plaque psoriasis. At baseline and throughout the study, the severity of disease for the psoriatic lesions was assessed using the Physician Global Assessment (PGA) score and a target lesion was assessed using the Total Lesion Severity Score (TLSS). A designated psoriatic plaque lesion was selected as the target lesion upon enrollment and evaluated throughout the study to determine the TLSS. To qualify for study entry, the subject needed to exhibit a PGA score of 3 (moderate) or 4 (severe) for overall disease severity, and a target lesion with an area of at least 5 cm(2) that achieved a combined score TLSS of >=7, with a plaque elevation score of >=3 (at least moderate). The mean % BSA affected by psoriasis ranged from 13%-17% at baseline. In both Phase 3 studies, a statistically significantly greater percentage of subjects in the desoximetasone spray 0.25% compared to vehicle group achieved both Clinical Success and Treatment Success at Day 28. These results, which were the primary efficacy variables, demonstrated superior efficacy in the active study group for both overall improvement of plaque psoriasis (by PGA) and in the individual psoriasis lesion (by TLSS) designated at baseline as the most severely involved plaque (target lesion). Assessment of secondary efficacy variables in both Phase 3 studies showed that subjects receiving desoximetasone Spray 0.25% twice daily exhibited statistically significantly mean changes from Baseline to Day 28 in PGA, TLSS, and % BSA affected when compared to subjects receiving vehicle spray twice daily. Tolerability and safety were assessed at all study visits. No statistically significant differences were observed between study arms and no major safety signals related to AEs were noted. No stinging and burning were reported with the spray formulation. This Class I topical corticosteroid has shown to be safe and efficacious in moderate to severe plaque psoriasis.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Desoximetasona/uso terapêutico , Glucocorticoides/uso terapêutico , Psoríase/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Desoximetasona/administração & dosagem , Desoximetasona/efeitos adversos , Método Duplo-Cego , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Psoríase/patologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
20.
Recent Pat Nanotechnol ; 7(1): 26-40, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22747717

RESUMO

The applications of Pulsed Laser Deposition (PLD) for producing nanoparticles, nanostructures and nanocomposites coatings based on recently developed laser ablating techniques and their convergence are being reviewed. The problems of in situ synthesis of hybrid inorganic-organic nanocomposites coatings by these techniques are being discussed. The novel modification of PLD called Pulsed Laser Adaptive Deposition (PLAD) technique is presented. The in situ synthesized inorganic/organic nanocomposites coatings from Magnesium (Mg) alloy/Rhodamine B and Mg alloy/ Desoximetasone by PLAD are described. The trends, applications and future development of discussed patented methods based on the laser ablating technologies for producing hybrid nanocomposite coatings have also been discussed in this review.


Assuntos
Lasers , Nanocompostos/química , Ligas/química , Desoximetasona/química , Magnésio/química , Metais/química , Patentes como Assunto , Rodaminas/química
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