RESUMO
OBJECTIVE: To determine whether budesonide (Bud) and triamcinolone acetate (TA) cause DNA fractures in the nasal mucosa and septal cartilage cells through examinations using the comet assay technique. STUDY DESIGN: Prospective, controlled experimental study. SETTING: University hospital. METHODS: Septal mucosal epithelial and cartilage tissue samples were taken from 9 patients. Cell cultures were prepared from these samples. Then, budesonide and triamcinolone acetate active ingredients at 2 different doses of 0.2 and 10 µM were separately applied to the cell cultures formed from both tissues of each patient, except the control cell culture, for 7 days in one group and 14 days in one group. After the applications, genotoxic damage was scored with the comet assay technique and the groups were compared. RESULTS: In both the budesonide and triamcinolone acetate groups, the comet scores at low and high doses, on the 7th and 14th days were found to be significantly higher in both cartilage and epithelial tissue than in the control group. CONCLUSION: The study results showed that budesonide and triamcinolone acetate lead to a significantly high rate of genotoxic damage in both epithelial tissue and cartilage tissue.
Assuntos
Budesonida , Mucosa Nasal , Humanos , Estudos Prospectivos , Budesonida/toxicidade , Dano ao DNA , Triancinolona/toxicidade , CartilagemRESUMO
ATP-binding cassette subfamily C (ABCC) genes code for phase III metabolism proteins that translocate xenobiotic (e.g., particulate matter 2.5 (PM2.5)) and drug metabolites outside the cells. IL-6 secretion is related with the activation of the ABCC transporters. This study assesses ABCC1-4 gene expression changes and proinflammatory cytokine (IL-6, IL-8) release in human bronchial epithelial cells (BEAS-2B) exposed to PM2.5 organic extract, budesonide (BUD, used to control inflammation in asthmatic patients), and a cotreatment (Co-T: PM2.5 and BUD). A real-time PCR assay shows that ABCC1 was upregulated in BEAS-2B exposed after 6 and 7 hr to PM2.5 extract or BUD but downregulated after 6 hr of the Co-T. ABCC3 was downregulated after 6 hr of BUD and upregulated after 6 hr of the Co-T exposures. ABCC4 was upregulated after 5 hr of PM2.5 extract, BUD, and the Co-T exposures. The cytokine assay revealed an increase in IL-6 release by BEAS-2B exposed after 5 hr to PM2.5 extract, BUD, and the Co-T. At 7 hr, the Co-T decreases IL-6 release and IL-8 at 6 hr. In conclusion, the cotreatment showed an opposite effect on exposed BEAS-2B as compared with BUD. The results suggest an interference of the BUD therapeutic potential by PM2.5.
Assuntos
Budesonida/toxicidade , Material Particulado/toxicidade , Brônquios/citologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Reação em Cadeia da PolimeraseRESUMO
The most significant adverse effect of inhaled steroid administration in children is suppression of hypothalamic-pituitary-adrenal axis responsiveness and suppression of growth. This study evaluates the effects of inhaled corticosteroids on the growth plates in infant rats. Rats aged 10 days were divided into five groups. Low and high doses of budesonide and fluticasone propionate (50-200-250 mcg/day) were applied with a modified spacer for 10 days. The rat's tibias were then removed and the effects of the steroids on the growth plates were compared. Growth cartilage chondrocyte proliferation and apoptosis rates; IGF-1 and glucocorticoid receptor levels; and resting, proliferative, hypertrophic, and total zone (TZ) measurements were compared using immunohistochemical-staining methods. With high doses of fluticasone, growth plates were affected much more than with high doses of budesonide (p = 0.01). Fluticasone, particularly at a dose of 250 mcg, inhibited the growth plate with an intensive negative impact on all parameters.
Assuntos
Budesonida/toxicidade , Fluticasona/toxicidade , Lâmina de Crescimento/efeitos dos fármacos , Administração por Inalação , Animais , Animais Lactentes , Peso Corporal/efeitos dos fármacos , Budesonida/administração & dosagem , Divisão Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Relação Dose-Resposta a Droga , Fluticasona/administração & dosagem , Lâmina de Crescimento/química , Hipertrofia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/análise , Osteogênese/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores de Glucocorticoides/análise , Tíbia/efeitos dos fármacos , Tíbia/crescimento & desenvolvimentoRESUMO
OBJECTIVE: Lyophilized microparticles composed of budesonide (BDS), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and hydroxypropylmethylcellulose (HPMC) or sodium carboxymethylcellulose (CMC-Na) were developed for intranasal delivery and their characteristics were evaluated. MATERIALS AND METHODS: The particle size and morphology were assessed by mean diameter measurement and scanning electron microscopy (SEM) image, respectively. The solid-state of products was tested by X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). In vitro drug release and cytotoxicity to the primary human nasal epithelial (HNE) cells were also evaluated. RESULTS AND DISCUSSION: Lyophilized microparticles exhibited vanishment of crystallinity of drug in XRPD analysis, the enfeeblement of carbonyl (C=O) stretching bands of carboxyl group in BDS in FT-IR spectra and the disappearance of endothermic peak of drug in the results of DSC study. Based on the results of solid-state studies, BDS was existed as an amorphous form in the lyophilized microparticles. CD complexation enhanced drug solubility and release rate, and HPMC or CMC-Na also improved drug dissolution rates. Cytotoxicity of developed microparticles to the HNE cells was measured and their safety to HNE cell was identified. CONCLUSION: Developed microparticles can efficiently deliver insoluble drug, such as BDS, to the nasal epithelium and thus it may improve therapeutic efficacy in the respiratory tract.
Assuntos
Budesonida/administração & dosagem , Excipientes/química , Glucocorticoides/administração & dosagem , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Administração Intranasal , Budesonida/química , Budesonida/toxicidade , Varredura Diferencial de Calorimetria , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Excipientes/toxicidade , Liofilização , Glucocorticoides/química , Glucocorticoides/toxicidade , Humanos , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , beta-Ciclodextrinas/toxicidadeRESUMO
Celecoxib is a COX-2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma. Glucocorticoids are used in the treatment of inflammatory bowel disease. A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects. The prodrug systems introduced here involve forming a nitro-substituted acylsulfonamide group in the case of celecoxib and a nitro-substituted 21-ester for the glucocorticoids. Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species. The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco-2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs.
Assuntos
Antineoplásicos/química , Budesonida/química , Nitrobenzenos/química , Prednisolona/química , Pró-Fármacos/química , Pirazóis/química , Sulfonamidas/química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Budesonida/uso terapêutico , Budesonida/toxicidade , Células CACO-2 , Celecoxib , Permeabilidade da Membrana Celular/efeitos dos fármacos , Clostridium perfringens/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/toxicidade , Humanos , Lactonas/química , Nitrorredutases/metabolismo , Prednisolona/uso terapêutico , Prednisolona/toxicidade , Pró-Fármacos/uso terapêutico , Pró-Fármacos/toxicidade , Pirazóis/uso terapêutico , Pirazóis/toxicidade , Sulfonamidas/uso terapêutico , Sulfonamidas/toxicidadeRESUMO
The purpose of this study was to compare the toxicity of three marketed corticosteroid receptor agonists (mometasone furoate, budesonide, or flunisolide) to the stomach of female CD-1 mice following oral administration via the diet for up to 52 weeks, with a 16-week recovery period (budesonide and flunisolide). A range of tissues was examined by light microscopy, accompanied by clinical pathology measurements to assess anticipated corticosteroid effects as a surrogate marker of systemic drug exposure. Microscopic changes seen in the stomach with each corticosteroid included pyloric hyalinization. This previously unreported finding was investigated using histochemical and immunohistochemical techniques and was found to consist of hyalinized collagen, in association with increased immunohistochemical signal for transglutaminase-2 and osteopontin. The significance of the osteopontin finding is unclear; however, the ability of transglutaminase-2 to facilitate the formation of degradation resistant protein bonds implies this protein may be involved in the pathogenesis of this change. Furthermore, published evidence that transglutaminase-2 may be induced by a corticosteroid agonist raises the possibility that pyloric stomach hyalinization may be a class effect of corticosteroids via the action of this enzyme.
Assuntos
Corticosteroides/agonistas , Anti-Inflamatórios/toxicidade , Budesonida/toxicidade , Fluocinolona Acetonida/análogos & derivados , Hialina/metabolismo , Pregnadienodiois/toxicidade , Piloro/metabolismo , Administração Oral , Corticosteroides/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Budesonida/administração & dosagem , Feminino , Fluocinolona Acetonida/administração & dosagem , Fluocinolona Acetonida/toxicidade , Proteínas de Ligação ao GTP/metabolismo , Camundongos , Camundongos Endogâmicos , Microscopia Eletrônica , Furoato de Mometasona , Osteopontina/metabolismo , Pregnadienodiois/administração & dosagem , Proteína 2 Glutamina gama-Glutamiltransferase , Piloro/anatomia & histologia , Transglutaminases/metabolismoRESUMO
Small-sized (less than 150 nm) long-circulating liposomes (LCL) may be useful as drug-targeting vehicles for anti-inflammatory agents in arthritis, since they selectively home at inflamed joints after i.v. administration. Previously it was shown in experimental arthritis that encapsulation of glucocorticoids (GC) as water-soluble phosphate esters in PEG-liposomes resulted in a strong improvement of the anti-inflammatory effect as compared to the free drug. In the present study, we compared the therapeutic activity and adverse effects induced by 3 different GC encapsulated in LCL in an attempt to further optimize the therapeutic index of liposomal GC in arthritis. Our data showed that with GC (dexamethasone, budesonide) of higher potency than prednisolone, the therapeutic activity of liposomal GC can be increased. However, side effects at the level of body weight and hyperglycemia were noted, related to the sustained free GC level observed after injection of the liposomal GC. An inverse relationship with the clearance rate of the free GC in question was shown. This study stresses the importance of a high clearance rate of the GC to be encapsulated for achieving a maximal therapeutic index with liposomal GC. Therefore high-clearance GC, which until now are only applied in local treatment approaches, may be very useful for the development of novel, highly effective anti-inflammatory preparations for systemic treatment of inflammatory disorders.
Assuntos
Artrite Experimental/tratamento farmacológico , Budesonida/farmacologia , Dexametasona/farmacologia , Prednisolona/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Artrite Experimental/fisiopatologia , Peso Corporal/efeitos dos fármacos , Budesonida/administração & dosagem , Budesonida/toxicidade , Dexametasona/administração & dosagem , Dexametasona/toxicidade , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacologia , Glucocorticoides/toxicidade , Hiperglicemia/induzido quimicamente , Lipossomos , Masculino , Tamanho da Partícula , Prednisolona/administração & dosagem , Prednisolona/toxicidade , Ratos , Ratos Endogâmicos LewRESUMO
UNLABELLED: The goal of this study was to compare the effects of liposomal and free glucocorticoid formulations on joint inflammation and activity of the hypothalamic-pituitary-adrenal (HPA) axis during experimental antigen-induced arthritis (AIA). A dose of 10mg/kg liposomal prednisolone phosphate (PLP) gave a suppression of the HPA-axis, as measured by plasma corticosterone levels in mice with AIA and in naïve mice. In a subsequent dose-response study, we found that a single dose of 1mg/kg liposomal prednisolone phosphate (PLP) was still equally effective in suppressing joint inflammation as 4 repeated once-daily injections of 10mg/kg free PLP. Moreover, the 1mg/kg liposomal PLP dose gave 22% less suppression of corticosterone levels than 10mg/kg of liposomal PLP at day 14 of the AIA. In order to further optimize liposomal glucocorticoids, we compared liposomal PLP with liposomal budesonide phosphate (BUP) (1mg/kg). At 1 day after treatment, liposomal BUP gave a significantly stronger suppression of joint swelling than liposomal PLP (lip. BUP 98% vs. lip. PLP 79%). Both formulations also gave a strong and lasting suppression of synovial infiltration in equal amounts. However, at day 21 after AIA, liposomal PLP still significantly suppressed corticosterone levels, whereas this suppression was not longer statistically significant for liposomal BUP. CONCLUSION: Liposomal delivery improves the safety of glucocorticoids by allowing for lower effective dosing. The safety of liposomal glucocorticoid may be further improved by encapsulating BUP rather than PLP.
Assuntos
Artrite Experimental/tratamento farmacológico , Budesonida/administração & dosagem , Glucocorticoides/administração & dosagem , Prednisolona/análogos & derivados , Animais , Antígenos/toxicidade , Artrite Experimental/patologia , Budesonida/farmacologia , Budesonida/toxicidade , Corticosterona/sangue , Relação Dose-Resposta a Droga , Glucocorticoides/farmacologia , Glucocorticoides/toxicidade , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prednisolona/administração & dosagem , Prednisolona/farmacologia , Prednisolona/toxicidade , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologiaRESUMO
The purpose of this research was to generate, characterize, and investigate the in vivo efficacy of budesonide (BUD) microparticles prepared by spray-drying technology with a potential application as carriers for pulmonary administration with sustained-release profile and improved respirable fraction. Microspheres and porous particles of chitosan (drug/chitosan, 1:2) were prepared by spray drying using optimized process parameters and were characterized for different physicochemical parameters. Mass median aerodynamic diameter and geometric standard deviation for conventional, microspheres, and porous particles formulations were 2.75, 4.60, and 4.30 microm and 2.56, 1.75, and 2.54, respectively. Pharmacokinetic study was performed in rats by intratracheal administration of either placebo or developed dry powder inhalation (DPI) formulation. Pharmacokinetic parameters were calculated (Ka, Ke, T(max), C(max), AUC, and Vd) and these results indicated that developed formulations extended half life compared to conventional formulation with onefold to fourfold improved local and systemic bioavailability. Estimates of relative bioavailability suggested that developed formulations have excellent lung deposition characteristics with extended T(1/2) from 9.4 to 14 h compared to conventional formulation. Anti-inflammatory activity of BUD and developed formulations was compared and found to be similar. Cytotoxicity was determined in A549 alveolar epithelial cell line and found to be not toxic. In vivo pulmonary deposition of developed conventional formulation was studied using gamma scintigraphy and results indicated potential in vitro-in vivo correlation in performance of conventional BUD DPI formulation. From the DPI formulation prepared with porous particles, the concentration of BUD increased fourfold in the lungs, indicating pulmonary targeting potential of developed formulations.
Assuntos
Antiasmáticos/administração & dosagem , Budesonida/administração & dosagem , Administração por Inalação , Aerossóis , Animais , Antiasmáticos/farmacocinética , Antiasmáticos/toxicidade , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Budesonida/farmacocinética , Budesonida/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Preparações de Ação Retardada , Dessecação , Excipientes , Humanos , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Microscopia Eletrônica de Varredura , Microesferas , Nanopartículas , Tamanho da Partícula , Polietilenoglicóis , Cintilografia , Ratos , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
OBJECTIVE: To measure the influence of topical steroids and the preservative potassium sorbate on the ciliary beat frequency (CBF) of human nasal mucosa in vitro. DESIGN: In vitro study of cultured ciliated cells of human nasal mucosa. METHODS: Human nasal mucosa was removed endoscopically and cultured for 10 days. Cell cultures with ciliated cells grown on an object slide were exposed to benzalkonium chloride and topical steroids in an exposure chamber. The CBF was measured with a photometer. RESULTS: The preservative potassium sorbate did not influence CBF in different concentrations. The glucocorticoid budesonide spray containing potassium sorbate did not affect CBF at 10% dilution and showed moderate reversible decrease of CBF at 50% dilution. The glucocorticoid sprays fluticasone propionate and mometasone fuorate containing the preservative benzalkonium chloride caused a reversible decrease of CBF at 10% dilution and a complete irreversible standstill at 50% dilution. CONCLUSIONS: In vitro, the steroid sprays containing fluticasone or mometasone, both with benzalkonium chloride, caused slowing or standstill of CBF depending on the concentration. The isolated preservative potassium sorbate and the budesonide nasal spray containing this preservative did not have negative influence on CBF in vitro. Potassium sorbate can therefore be considered harmless to the motility of ciliated cells.
Assuntos
Anti-Inflamatórios/toxicidade , Glucocorticoides/toxicidade , Depuração Mucociliar/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Conservantes Farmacêuticos/toxicidade , Administração por Inalação , Aerossóis , Androstadienos/toxicidade , Compostos de Benzalcônio/toxicidade , Budesonida/toxicidade , Técnicas de Cultura , Relação Dose-Resposta a Droga , Fluticasona , Humanos , Furoato de Mometasona , Pregnadienodiois/toxicidade , Ácido Sórbico/toxicidadeRESUMO
Administration of antiasthmatic drugs in the form of inhalation particles may alter the cytokine network in the airways, independently of their pharmacological actions. Changes induced by drugs not well tolerated may potentially contribute to the immunopathology of the disease, a strongly undesirable effect. In this study, cell viability assays and characterization of the cellular profile of cytokines and chemokines were performed in order to investigate the response of human bronchoalveolar macrophages and bronchial epithelial cells in culture to inhalation particles of the cyclosporine derivative IMM 125. Interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and IL-8 were assayed by enzyme-linked immunosorbent assay (ELISA) in the supernatants of bronchoalveolar macrophages, and RANTES, granulocyte--macrophage colony-stimulating factor (GM-CSF), and IL-8 in those of bronchial epithelial cells. Cells were studied both under basal and stimulated conditions (lipopolysaccharide and TNFalpha were used for activating macrophages and epithelial cells, respectively). The immunosuppressant FK 506 and the glucocorticoid Budesonide served as comparison. IMM 125 did not affect cell viability (except at high concentrations and long time periods). Moreover, IMM 125 did not induce an increase in the secretion of any of the cytokines and chemokines measured with respect to nontreated cells, except for a slight increase in IL-8, an effect that was also observed for FK 506, Budesonide, and inert latex particles, and was therefore regarded as nonspecific. Furthermore, IMM 125 significantly decreased the secretion of TNFalpha, IL-1beta by macrophages, and GM-CSF by epithelial cells, suggesting an antiinflammatory potential. In conclusion, the present in vitro results point to a good tolerance of human airways to IMM 125 inhalation particles.
Assuntos
Antiasmáticos/toxicidade , Líquido da Lavagem Broncoalveolar/citologia , Ciclosporinas/toxicidade , Citocinas/metabolismo , Células Epiteliais/metabolismo , Macrófagos/metabolismo , Administração por Inalação , Antiasmáticos/efeitos adversos , Broncodilatadores/toxicidade , Budesonida/toxicidade , Membrana Celular/enzimologia , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Ciclosporinas/efeitos adversos , Humanos , Imunossupressores/toxicidade , L-Lactato Desidrogenase/metabolismo , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Tacrolimo/toxicidadeRESUMO
Therapy of acute intestinal GVHD is still one of the main challenges after allogeneic transplantation. Increasing systemic immunosuppression (IS) is the first choice and includes corticosteroids and lymphocyte antibodies, often associated with severe side-effects. In inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, topical steroid therapy is used very successfully. Because of the similarity between these and acute intestinal GVHD we conducted a trial with oral budesonide (Budenofalk), a new topically active glucocorticoid, to treat patients with acute GVHD > or = grade II. After a diagnosis of aGVHD > or = grade II, 22 patients received increased IS, mainly systemic corticosteroids, and additionally budesonide 9 mg/day divided into three doses. Improvement in aGVHD, infectious side-effects, reduction of systemic IS and outcome were documented. Results were compared with the results of 19 control patients, who were treated only by increasing IS dose. In 17/22 patients (70%), treated with budesonide, the acute intestinal GVHD resolved and no relapse occurred after decreasing the systemic IS, while continuing budesonide. In only 8/19 patients in the control group did the acute intestinal GVHD resolve and 2/8 patients had a relapse of intestinal GVHD after decreasing IS, with an overall response of 33%. No severe intestinal infections occurred. We conclude that budesonide may be effective in acute intestinal GVHD as a topical corticosteroid and prospective, randomized studies should demonstrate its efficacy in allowing reduction of systemic immunosuppressive therapy, and its side-effects.
Assuntos
Corticosteroides/administração & dosagem , Budesonida/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Enteropatias/tratamento farmacológico , Doença Aguda , Administração Tópica , Adolescente , Corticosteroides/uso terapêutico , Adulto , Terapia Comportamental , Transplante de Medula Óssea , Budesonida/toxicidade , Criança , Endoscopia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Terapia de Imunossupressão , Enteropatias/imunologia , Masculino , Pessoa de Meia-Idade , Relações entre Irmãos , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
Ear edema models are regularly used for topical testing of antiinflammatory compounds. However, test compounds are usually applied simultaneously with proinflammatory agents at the same site which may result in mutual interactions. In order to avoid the occurrence of false antiinflammatory effects, a model of oxazolone-induced contact hypersensitivity has been described in which the hapten and test compound are each applied separately to only one side of the ear. By splitting and weighing the dorsal and ventral cutis of the ears, it was shown that the edemateous response of the control nonhapten side was comparable with the hapten-treated side. Some agents with antiinflammatory properties, as for example, dapsone, cimetidine, cyclosporine A, and budesonide, were tested simultaneously with oxazolone on both sides of the ear or applied separately on the dorsal and ventral ear sides, respectively. When dissolving the compounds in solutions of oxazolone, marked colorations of the test solutions were noted, indicating the occurrence of a chemical interaction. On simultaneous application at the same area, almost complete inhibition of the edemateous response was obtained for all compounds tested. In contrast, when applied separately, only budesonide appeared to exhibit antiinflammatory activity. The results indicate that the proposed model can be used to avoid the occurrence of interactions between oxazolone, and possibly other sensitizers, and substances that are being evaluated for topical antiinflammatory activity. By use of this model spurious antiinflammatory activity can be detected.