pulmicort and Edema

Budesonide (Bud) is a nonhalogenated glucocorticoid with high anti-inflammatory potency and low systemic side effects. However, the poor water solubility of Bud affects its dissolution and release behavior, thus influencing its anti-inflammatory effect. This study was aimed at synthesizing and evaluating novel conjugates of Bud, hoping to increase the anti-inflammatory activity of Bud by improving its water solubility.. Seven novel Bud conjugates (. As compared to Bud, the equilibrium solubility of. The amino acid ester compounds budesonide-21-glycine ester (

Topics: A549 Cells; Animals; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Cell Survival; Ear Diseases; Edema; Humans; Interleukin-6; Male; Mice; Mice, Inbred Strains; Molecular Structure; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Xylenes

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Budesonide; Diagnosis, Differential; Drug Hypersensitivity; Edema; Female; Humans; Hypersensitivity, Immediate; Lip Diseases; Middle Aged

Topics: Acute Lung Injury; Adrenal Cortex Hormones; Animals; Apoptosis; Biomarkers; Bronchoalveolar Lavage Fluid; Budesonide; Caspase 3; Disease Models, Animal; Edema; Epithelial Cells; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Lung; Oxidative Stress; Oxygen; Rabbits; Tumor Necrosis Factor-alpha; Ventilation

A 7-year-old male patient who had abdominal swelling and eyelid oedema was diagnosed with restrictive cardiomyopathy. His serum albumin level was 2.3 g/dl. Protein-losing enteropathy due to restrictive cardiomyopathy was diagnosed and oral budesonide was started. His serum albumin level began to rise and ascites and peripheric oedema disappeared. The patient underwent a successful cardiac transplantation and budesonide was stopped. After the heart transplantation, the albumin level decreased to 2.3 g/dl, and therefore it was restarted. When the serum albumin level increased, the budesonide dose was tapered and stopped in 1 month. Budesonide may be an effective drug in patients with protein-losing enteropathy due to heart failure.

Topics: Administration, Oral; Ascites; Budesonide; Cardiomyopathy, Restrictive; Child; Edema; Glucocorticoids; Heart Transplantation; Humans; Male; Protein-Losing Enteropathies; Serum Albumin; Treatment Outcome

Topics: Adolescent; Biopsy, Needle; Budesonide; Crohn Disease; Diagnosis, Differential; Edema; Follow-Up Studies; Genital Diseases, Male; Granuloma; Humans; Immunohistochemistry; Lymphangitis; Male; Penile Diseases; Risk Assessment; Scrotum; Severity of Illness Index

In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17alpha-dichloroacetoxy-11beta-hydroxyandrosta-1,4-diene-3-one-17beta-carboxylate), a new soft steroid, intended to use for the treatment of asthma, were investigated in an animal model of allergen sensitized and challenged Brown Norway rats using local treatment. The examinations involved the determination of the effect of the compound on the extent of allergen induced broncho-alveolar fluid and lung tissue eosinophilia, goblet cell hyperplasia and mucus production, perivascular edema formation, and airways hyperresponsiveness. The activity of etiprednol dicloacetate was compared with that of budesonide. Using in vitro methods, the soft character of etiprednol dicloacetate was investigated together with its capability to dissociate transrepressing and transactivating properties. We found that combining all the examined parameters etiprednol dicloacetate was at least equipotent with budesonide in the animal model, but in several investigated variables it surpassed the activity of budesonide. The effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of the serum, present in the assay, it was also strongly affected by the incubation time and decreased significantly when it was preincubated with human plasma. These features are characteristics of a soft drug that is quickly inactivated in the systemic circulation. In addition, it was revealed that while the transrepressing potential of etiprednol dicloacetate remained high, its transactivating activity was greatly reduced. These data indicate that the strong local effect of the compound will very likely be accompanied with a significantly reduced systemic activity predicting favorable selectivity in the pharmacological action of etiprednol dicloacetate.

Topics: Adrenal Cortex Hormones; Allergens; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchodilator Agents; Budesonide; Disease Models, Animal; Edema; Epithelial Cells; Glucocorticoids; Humans; Male; Neutrophil Infiltration; Rats; Time Factors; Transcriptional Activation

The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Barton ester decarboxylation and trapping the generated 17-radical with butyrolactone disulfides. The glucocorticoid butyrolactones were hydrolyzed in human plasma by the enzyme paraoxonase to the respective hydroxy acids, which were very weak glucocorticoid agonists. The rate of hydrolysis in plasma was very rapid (t1/2 = 4-5 min) in the case of lactones possessing a sulfur atom in the alpha-position of the butyrolactone group, whereas carbon-linked lactones were stable in plasma. 16alpha,17alpha-Butylidenes were more potent glucocorticoid agonists than the corresponding isopropylidene derivatives. Similarly, 1,4-dien-3-ones were more potent than the corresponding 4-en-3-ones. The butyrolactones linked to the steroidal nucleus via the beta-position were more potent glucocorticoid agonists than those linked through the alpha-position of the lactone. The most potent compounds were also shown to be stable in human lung S9 fraction, showed much lower systemic effects than budesonide in the thymus involution test, and possessed topical antiinflammatory activity in the rat ear edema model.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Butyrates; Chromatography, High Pressure Liquid; Drug Stability; Edema; Glucocorticoids; HeLa Cells; Humans; In Vitro Techniques; Lactones; Lung; Male; Organ Size; Rats; Receptors, Glucocorticoid; Structure-Activity Relationship; Thymus Gland

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.

Topics: Adjuvants, Immunologic; Animals; Artifacts; Budesonide; Dermatitis, Contact; Disease Models, Animal; Drug Interactions; Ear; Edema; False Positive Reactions; Female; Haptens; Mice; Mice, Inbred BALB C; Organ Size; Oxazolone; Toxicity Tests

The antiinflammatory effect of topically applied budesonide ointment on carrageenin induced paw edema in rats, croton oil induced ear edema in rats, passive cutaneous anaphylaxis (PCA) in rats and picrylchloride induced contact hypersensitivity in mice was studied and compared with those of commercially available ointments containing betamethasone 17-valerate, hydrocortisone 21-acetate, hydrocortisone 17-butyrate or fluocinonide. The five ointments had almost the same degree of activity against the carrageenin induced paw edema. Budesonide ointment was strongest in inhibiting the croton oil induced ear edema. Budesonide and fluocinonide ointments were stronger than the other 3 ointments in inhibiting PCA and picrylchloride induced hypersensitivity. No clear atrophic effect on the thymus or adrenal was observed with any of the ointments at the doses tested. When the effect of budesonide ointment was compared with that of budesonide cream, there were no differences in activity between the two formulations. The results suggest that budesonide is a useful drug with a superior topical antiinflammatory activity.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Budesonide; Dermatitis; Dermatitis, Contact; Edema; Emulsions; Mice; Mice, Inbred ICR; Ointments; Passive Cutaneous Anaphylaxis; Pregnenediones; Rats; Rats, Inbred Strains

The use of topical glucocorticosteroid therapy on large skin areas or in the lung is sometimes restricted by the occurrence of unwanted, general corticoid actions owing to a profound systemic absorption. To decrease this risk potent glucocorticoids with an enhanced ratio between their topical and their systemic glucocorticoid potencies are wanted. Therefore, structure-activity studies were performed in rat models to investigate what influences the type of substitution in the 16 alpha, 17 alpha-acetal group and the introduction of fluorine in the 9 alpha- or the 6 alpha, 9 alpha-positions have on the topical and the systemic activities, respectively. The introduction of an unsymmetrical 16 alpha, 17 alpha-acetal group (named acetal type B) markedly enhanced the topical anti-inflammatory potency compared with that of the conventional 16 alpha, 17 alpha-acetonide group (named acetal type A). Both acetal types had a similar systemic glucocorticoid potency, however, 9 alpha-Fluoro and especially 6 alpha, 9 alpha-difluoro substitution, on the other hand, enhanced the systemic glucocorticoid activity more than they raised the topical anti-inflammatory potency. Optimal topical to systemic activity ratio was obtained with a nonhalogenated corticoid of acetal type B structure. This compound, budesonide, had at least the same high topical anti-inflammatory potency as fluocinolone acetonide but was about 10 times less potent than this reference to induce systemic glucocorticoid actions. Its lower systemic activity is probably due to a more rapid biotransformation in the liver.

Topics: Acetals; Administration, Topical; Animals; Anti-Inflammatory Agents; Budesonide; Ear Diseases; Edema; Fluorine; Glucocorticoids; Humans; Male; Organ Size; Pregnenediones; Rats; Rats, Inbred Strains; Skin; Structure-Activity Relationship; Thymus Gland