(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Intestinal-Diseases

A major aetiologic role for foods has been demonstrated in urticaria, atopic eczema and dermatitis herpetiformis. In some patients with urticaria, whealing occurs within minutes of the ingestion of a particular food. In most, but not necessarily all cases, this appears to be a consequence of IgE-mediated cutaneous mast cell degranulation, i.e. a classical type I hypersensitivity response. In other patients with recurrent urticaria, the whealing may be provoked by foods by a much slower and more insidious reaction. This type of reaction has been established in the case of several common food additives, notably azo dyes, but other foods may be able to cause urticaria in a similar fashion. Foods appear to play an important provocative role in many patients with atopic eczema. The reaction in such cases appears to be slow and insidious, almost always unrecognized by the patient and not detected by skin testing or tests for IgE antibodies. There can be no real doubt that dietary gluten is responsible for most, if not all dermatitis herpetiformis, though this relationship was revealed only by the finding of concurrent and usually asymptomatic jejunal villous atrophy in affected individuals. The mechanisms responsible for the slow food reactions in urticaria, atopic eczema and dermatitis herpetiformis remain largely unknown, but are likely to be different in each case.

Topics: Aging; Animals; Azo Compounds; Beclomethasone; Benzoates; Cattle; Child; Child, Preschool; Dermatitis Herpetiformis; Dermatitis, Atopic; Eggs; Food Additives; Food Hypersensitivity; Glutens; Humans; Immunoglobulin A; Immunoglobulin E; Infant; Infant, Newborn; Intestinal Diseases; Milk; Skin Diseases; Sulfones; Time Factors; Urticaria

In this study, we investigated the level of gut absorption following oral beclomethasone dipropionate (BDP) administration by measuring the blood concentration of its metabolites measured by LC-MS/MS using the HPLC method. Five patients who were administered BDP orally for gut GVHD were included. The blood concentrations of beclomethasone-17-monopropionate (17BMP), which is one of the active metabolites of BDP, were 618 approximately 1, 749 pg/mL in 4 of the studied 5 patients, which was comparable to that after inhalation of BDP; however, it was relatively higher in one patient (2,439+/-161 pg/mL). As the blood concentration of 17BMP in this study patient was higher compared with healthy volunteers administered a single oral BDP 4 mg, GVHD patients might have a higher concentration than healthy volunteers. Given that a higher grade of gut GVHD was associated with a higher blood level of 17BMP, BDP absorption might be associated with gut mucosal injury. Thus, the systemic adverse effect following oral BDP administration might not be negligible especially in gut GVHD patients.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Female; Graft vs Host Disease; Humans; Intestinal Absorption; Intestinal Diseases; Male; Middle Aged

Intestinal graft-versus-host disease (GVHD) causes anorexia, vomiting, abdominal pain, and diarrhea. We investigated oral beclomethasone dipropionate (BDP), a potent, topically active corticosteroid, as therapy for this disease. Forty-two allogeneic marrow-graft recipients with biopsy-proven intestinal graft-versus-host disease of mild-to-moderate severity received BDP (8 mg daily) for up to 28 days. Weekly symptom scores, oral intake, and surveillance throat and stool cultures were compared with baseline values. Adrenal testing was performed serially in patients not receiving concurrent prednisone. Improvement was seen in appetite (P < 0.001), oral intake (P < 0.001), nausea (P = 0.013), and diarrhea (P = 0.02) over the course of therapy, and an overall beneficial response was observed in 72% of 40 evaluable patients. Surveillance cultures of throat and stool showed no increase in bacterial or fungal colonization over time. The adrenal axis became suppressed in 11 of 20 evaluable patients (55%) but suppression was not a prerequisite for clinical response, as 6 of 9 patients who retained normal adrenal function improved clinically. We conclude that oral BDP is a safe and effective treatment for mild-to-moderate intestinal graft-versus-host disease. Systemic absorption probably occurs, but adrenal suppression is not a prerequisite for clinical efficacy, suggesting that the biological effect is primarily topical. BDP should be further investigated as a topical therapy for intestinal GVHD.

Topics: Administration, Oral; Adrenocorticotropic Hormone; Anti-Inflammatory Agents; Beclomethasone; Graft vs Host Disease; Humans; Hydrocortisone; Immunosuppressive Agents; Intestinal Diseases; Patient Compliance; Prednisone

Topics: Abdomen; Adrenoleukodystrophy; Beclomethasone; Child; Glucocorticoids; Graft vs Host Disease; Humans; Intestinal Diseases; Male; Nitriles; Pyrazoles; Pyrimidines; Stem Cell Transplantation; Ultrasonography; Ultrasonography, Doppler, Color

Graft-versus-host disease (GVHD) is a major concern in transplantation patients. Gut GVHD is accompanied by diarrhea, abdominal pain, and/or melena. Although oral treatment with corticosteroids (CSs) is effective in treating gut GVHD, it can cause adverse reactions that affect the entire body. Topical administration of CSs can be effective in treating diseases in which lesions are limited locally, because adverse reactions can then be alleviated. In this study, we examine and discuss an enteric-coated beclomethasone dipropionate (BDP) capsule (BDP-EC) formulated at Okayama University Hospital. The BDP-EC did not dissolve in solution 1 (pH1.2), and began disintegrating in solution 2 (pH6.8) after 5min, with a mean dissolution rate at 15min of 85%. We then used the capsule to treat a patient who developed gut GVHD after allogeneic hematopoietic stem cell transplantation. Clinically, the frequency of diarrhea decreased after BDP-EC administration. In addition, we were able to decrease the prednisolone equivalent dose. Symptoms associated with adverse reactions to BDP were not observed during the hospitalization period. These findings suggest that the administration of BDP-EC in the early stages of gut GVHD may allow a reduction in the initial doses of systemic CSs.

Topics: Aged; Beclomethasone; Capsules; Glucocorticoids; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Intestinal Diseases; Leukemia-Lymphoma, Adult T-Cell; Male; Tablets, Enteric-Coated; Transplantation, Homologous

The ability of four drugs with anti-allergic action to modulate the uptake of bystander protein, lactulose/rhamnose permeability ratios and mast cell activation was studied in rats presensitized with egg albumin in alum and challenged intraduodenally with the same antigen. Beclomethasone dipropionate (BDP) and nedocromil both significantly reduced the uptake of the bystander protein, bovine serum albumin (P < 0.002 and P > 0.02 respectively). BDP also significantly reduced sugar permeability (P < 0.01). In animals with elevated lactulose/rhamnose permeability ratios we confirmed our earlier observation of a significant correlation between levels of the specific mucosal mast cell protease Rat Chymase II (RChyII-previously known as RMCPII) and the sugar ratios. None of the drugs had any influence on the levels of mast cell protease II released following challenge and there was no correlation between the histological light microscopic appearance of the mast cells and the experimental treatment administered. Our results suggest that in the gut the pharmacological effect of anti-allergic drugs may be complex. Some, such as nedocromil, appear to act only on the mechanisms underlying increased protein uptake whereas others, such as BDP, appear to abrogate both increased protein uptake and increased sugar permeability.

Topics: Animals; Anti-Inflammatory Agents; Beclomethasone; Bronchodilator Agents; Cell Membrane Permeability; Chymases; Cromolyn Sodium; Duodenum; Hypersensitivity; Intestinal Absorption; Intestinal Diseases; Intestinal Mucosa; Jejunum; Lactulose; Mast Cells; Nedocromil; Rats; Rats, Sprague-Dawley; Rhamnose; Serine Endopeptidases; Serum Albumin, Bovine; Thioxanthenes; Xanthones