pulmicort and Body-Weight

Intranasal budesonide is an efficacious treatment for perennial allergic rhinitis. Long-term effects on safety, particularly in children, need further investigation.. To investigate the long-term safety of intranasal budesonide in children.. In an open trial, 78 children (5-15 years) with perennial rhinitis were treated with intranasal budesonide pressurized metered dose inhaler 200 microg twice daily (delivered daily dose 256 microg) for 12 months; 43 children stayed in the study for 12 additional months and were switched to aqueous suspension (400 microg delivered daily dose) for 6 months. Statural growth, bone age, ophthalmologic and rhinoscopic status, cortisol and biochemical analyses in blood and urine were monitored during the first and second years, and adverse events (AEs) were continuously recorded.. No significant effects on statural growth and bone age, compared with reference values, were observed. Morning plasma cortisol and 24-h urinary cortisol were not changed during treatment. Patients reported 195 AEs, most commonly nasal dryness (30%), blood-tinged secretions (21%) and, among non-nasal AEs, headache (13%). Rhinoscopy revealed no signs of mucosal atrophy, ulceration, or candidiasis but some nasal dryness. No treatment-related ophthalmological or biochemical aberrations were found. Reduction of blood eosinophils and nasal symptom scores, compared with pre-treatment values, indicated the efficacy of budesonide treatment.. Long-term treatment for 1-2 years with intranasal budesonide 256-400 microg daily in children with perennial rhinitis revealed no negative effects on growth or endogenous cortisol production. Local side-effects were mild and patient symptoms decreased.

Topics: Administration, Intranasal; Adolescent; Body Height; Body Weight; Bone Development; Budesonide; Child; Child, Preschool; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Rhinitis, Allergic, Perennial; Time Factors

Leptin, a 167-amino-acid peptide, is a recently discovered hormone which is believed to play a major role in the regulation of body weight. Systemic administration of exogenous glucocorticoids has been found to increase circulating leptin levels. In this study, we aimed to assess serum leptin in children with asthma treated with inhaled budesonide 800 micrograms day-1. Ten boys and three girls with asthma, all adolescents aged from 12.9 to 16.6 years, were studied in a randomized double-blind two-period cross-over trial with 4-week treatment periods and a 1-week wash out. Placebo was given during one period and 800 micrograms budesonide during the other via a 750 ml volume spacer (Nebuhaler, Astra Draco, Lund, Sweden). On the last day of the placebo and budesonide periods blood samples were taken and serum leptin was measured by a specific radioimmunoassay. The difference in mean (SEM) leptin concentration between the budesonide and placebo period was 0.2 (0.4) microgram l-1 (P = 0.71; t = -0.4; df = 12, 95% confidence interval -0.9-0.7 microgram l-1). Inhaled budesonide 800 micrograms per day from a Nebuhaler does not influence circulating leptin levels, suggesting that regulation of body weight is unaffected.

Topics: Administration, Topical; Adolescent; Anti-Inflammatory Agents; Appetite; Asthma; Biomarkers; Body Weight; Budesonide; Child; Cross-Over Studies; Double-Blind Method; Female; Glucocorticoids; Humans; Leptin; Male; Proteins

In a controlled prospective study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide and compared these findings with those obtained from children not treated with corticosteroids. Two hundred and sixteen children were followed at 6 monthly intervals for 1-2 years without inhaled budesonide and then for 3-6 years on inhaled budesonide. Sixty-two children treated with theophylline, beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3-7 years (controls). During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms (P < 0.01) and no signs of tachyphylaxis to the treatment were seen. Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma (from 0.03 to 0.004 per child, P < 0.001). In patients not treated with budesonide an annual decrease in % predicted FEV1 of 1-3% was seen. In contrast FEV1 improved significantly with time during budesonide treatment, both compared with the run-in period and with the control group (P < 0.01). Furthermore, there was a significant (P = 0.01) relationship between the duration of asthma at the start of budesonide and the annual increase in FEV1 during budesonide therapy. After 3 years of treatment with budesonide, children who started this therapy later than 5 years after the onset of asthma had significantly lower FEV1 (96%) than the children who received budesonide within the first 2 years after the onset of asthma (101%) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Topical; Anti-Inflammatory Agents; Asthma; Body Height; Body Weight; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Administration Schedule; Female; Glucocorticoids; Growth; Humans; Lung; Male; Pregnenediones; Prospective Studies; Pulmonary Ventilation

The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, we proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The developed Mn-NLCs were characterized for particle size and size distribution, zeta potential, %entrapment efficiency, FTIR and TEM analysis. Furthermore, to ensure delivery of developed cargo to the colonic region, the Mn-NLCs were encapsulated using Eudragit

Topics: Body Weight; Budesonide; Cell Line; Cell Survival; Colon; Drug Carriers; Drug Liberation; Engineering; Humans; Inflammatory Bowel Diseases; Kinetics; Lipids; Mannose; Nanoparticles; Organ Size; Surface Properties

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.

Topics: Administration, Inhalation; Animals; Animals, Suckling; Body Weight; Budesonide; Cell Division; Chondrocytes; Dose-Response Relationship, Drug; Fluticasone; Growth Plate; Hypertrophy; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Osteogenesis; Pituitary-Adrenal System; Random Allocation; Rats; Rats, Wistar; Receptors, Glucocorticoid; Tibia

Various therapeutic regimes have been proposed with limited success for treatment of phosgene-induced acute lung injury (P-ALI). Corticoids were shown to be efficacious against chlorine-induced lung injury but there is still controversy whether this applies also to P-ALI. This study investigates whether different regimen of curatively administered budesonide (BUD, 10 mg/kg bw, i.p. bid; 100 mg/m(3)×30 min, nose-only inhalation), mometasone (MOM, 3 mg/kg bw, i.p. bid) and dexamethasone (DEX, 10, 30 mg/kg bw, i.p. bid), show efficacy to alleviate P-ALI. Efficacy of drugs was judged by nitric oxide (eNO) and carbon dioxide (eCO2) in exhaled air and whether these non-invasive biomarkers are suitable to assess the degree of airway injury (chlorine) relative to alveolar injury (phosgene). P-ALI related analyses included lung function (enhanced pause, Penh), morbidity, increased lung weights, and protein in bronchial alveolar lavage fluid (BALF) one day postexposure. One of the pathophysiological hallmarks of P-ALI was indicated by increased Penh lasting for approximately 20 h postexposure. Following the administration of BUD, this increase could be suppressed; however, without significant improvement in survival and lung edema (increased lung weights and BALF-protein). Collectively, protocols shown to be efficacious for chlorine (Chen et al., 2013) were ineffective and even increased adversity in the P-ALI model. This outcome warrants further study to seek for early biomarkers suitable to differentiate chlorine- and phosgene-induced acute lung injury at yet asymptomatic stage. The patterns of eNO and eCO2 observed following exposure to chlorine and phosgene may be suitable to guide the specialized clinical interventions required for each type of ALI.

Topics: Acute Lung Injury; Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Biomarkers; Body Weight; Bronchoalveolar Lavage Fluid; Budesonide; Carbon Dioxide; Chemical Warfare Agents; Dexamethasone; Diet; Male; Mometasone Furoate; Nitric Oxide; Organ Size; Phosgene; Pregnadienediols; Rats; Rats, Wistar; Respiratory Function Tests; Respiratory Mechanics

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.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Body Weight; Budesonide; Dexamethasone; Glucocorticoids; Hyperglycemia; Liposomes; Male; Particle Size; Prednisolone; Rats; Rats, Inbred Lew

Concurrent and sequential administration of combinations of budesonide, bexarotene, suberoylanilide hydroxamic acid (SAHA) and atorvastatin were evaluated in A/J mice for prevention of lung tumors initiated by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol, NNK).. Individual drugs and their combinations were administered for 26 weeks after NNK initiation. For sequential administration, budesonide was given for 21 weeks followed by a second drug.. Alone, budesonide, bexarotene, and SAHA caused a significant decrease in total and large tumors at 21 and 26 weeks. Concurrent treatment with budesonide and bexarotene or SAHA caused a significantly greater decrease in total tumors and large tumors than either drug administered alone. Sequential administration of all combinations (except budesonide/atorvastatin) gave a significant reduction in total and large tumors. Budesonide followed by SAHA and SAHA with atorvastatin yielded a greater reduction in large tumors.. Combinations of drugs demonstrated a greater efficacy in preventing mouse lung tumors than did the individual agents.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Bexarotene; Body Weight; Budesonide; Chemoprevention; Female; Hydroxamic Acids; Lung Neoplasms; Mice; Tetrahydronaphthalenes; Vorinostat

Biomarkers are being developed that can aid in the evaluation of cancer therapeutic and chemopreventive drugs. Two suggested biomarkers found in mouse lung tumors are DNA hypomethylation and alterations in mRNA expression of genes, such as 18S RNA, caspase 3, cyclin B2, cyclin E1, iNOS and survivin. Budesonide is very efficacious in preventing lung tumors in mice, so that its ability to modulate biomarkers in lung tumors was determined. Lung tumors were induced by vinyl carbamate in female strain A/J mice. Budesonide (2.0 mg/kg diet) was administered for 2, 7 and 21 days or for 14 days followed by a 7-days' holding period prior to the killing of the mice at week 27. After 2 days of budesonide treatment, the size of the lung tumors was reduced. Tumor size continued to decrease during the 21 days of treatment. In the tumors, 2 days of treatment resulted in (i) increased methylation of DNA, reversing DNA hypomethylation, (ii) increased expression of 18S RNA and (iii) decreased mRNA expression of caspase 3, cyclin B2, cyclin E1, iNOS and survivin. Termination of budesonide treatment at 7 days prior to killing did not affect the size of the tumors, but did result in increased mRNA expression of the 5 genes, approaching the expression level in tumors from control mice. Hence, budesonide rapidly decreased the size of lung tumors, reversed DNA hypomethylation and modulated mRNA expression of genes; with the molecular alterations requiring continued treatment with the drug for maintenance.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers, Tumor; Body Weight; Budesonide; Caspase 3; Cell Proliferation; Cyclin B; Cyclin B2; Cyclin E; DNA Methylation; Female; Gene Expression; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Mice; Mice, Inbred Strains; Microtubule-Associated Proteins; Nitric Oxide Synthase Type II; Repressor Proteins; RNA, Messenger; RNA, Ribosomal, 18S; Survivin; Urethane

Neurotrophic factors and receptors are upregulated in the respiratory tract of humans and rodents infected by the respiratory syncytial virus, leading to airway inflammation and hyperreactivity. The contribution of neurotrophic pathways to the recruitment of immuno-inflammatory cells and their response to anti-inflammatory therapy remains unclear. We sought to determine whether selective nerve growth factor inhibition prevents the immuno-inflammatory response against infection, and explored the effect of inhaled corticosteroids on virus-induced neurotrophic upregulation and the consequent recruitment of immuno-inflammatory cells into the airways. We tried to inhibit the recruitment of lymphocytes and monocytes into the airways of infected weanling rats using immunologic inhibition of nerve growth factor with a specific blocking antibody, or chemical inhibition of receptor tyrosine kinase with K252a. The anti-inflammatory activity of inhaled corticosteroids was studied in infected rats treated with budesonide, fluticasone, or vehicle. Immunological or chemical inhibition of nerve growth factor or its high-affinity receptor tyrosine kinase pathway inhibited the recruitment of inflammatory cells triggered by nociceptive irritation of infected rat airways, thereby reducing local and systemic immuno-inflammatory responses against the virus. Neurotrophic upregulation in infected airways was not affected by inhaled corticosteroids. As a logical consequence, these commonly used drugs were also unable to stop the recruitment of immune and inflammatory effector cells into infected airways. Overexpression of neurotrophic factors and receptors in airways infected by respiratory syncytial virus is critical for the development of airway inflammation and hyperreactivity, which is resistant to the anti-inflammatory effect of inhaled corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Animals; Body Weight; Bronchoalveolar Lavage Fluid; Bronchodilator Agents; Budesonide; Carbazoles; Drug Resistance; Enzyme Inhibitors; Female; Fluticasone; Indole Alkaloids; Male; Nerve Growth Factors; Pneumonia; Rats; Rats, Inbred F344; Receptor Protein-Tyrosine Kinases; Respiratory Syncytial Virus Infections; Steroids; Up-Regulation

To determine broadband ultrasound attenuation (BUA) and speed of sound (SOS) on the os caicis in asthmatic children. To correlate these findings with sex, age, weight and height, topical steroid intake, and asthma severity grade (ASG).. 178 children (ASG 1 - 3)/(98 m, 80 f; mean age 11.9 +/- 3.1 y) were consecutively chosen from 4/00 to 9/01. Children with any other chronic disease were excluded. BUA and SOS were measured using SAHARA (Hologic lnc. Waltham, USA). Regional normative BUA and SOS data of 3 299 children (obtained with the same system), were used to calculate age-, weight- and height-matched standard-deviation-scores (SDS) for both sexes. Asthma severity grade and steroidal intake were determined. The highest topical steroid dosage was 500 micro g Fluticasone or 800 micro g Budesonide per day.. 10/178 children were small and 7/178 tall per age (5.6 %/3.9 %), 11/178 children were light (6.2 %) and 9 heavy per age (5.0 %). 19 and 45 children had reduced BUA and SOS values, respectively. The following rates of reduced values were observed: girls: BUA 15.0 % (12/80), SOS 25.0 % (20/80); boys: BUA 7.1 %, SOS 25.5 % (7/98 and 25/98). Sexual differences were not significant. Reduced SOS-values were associated with higher severity and occurred significantly more frequent at children under steroidal intake (0.09 vs. 0.25 [BUA] and - 0.37 vs. - 0.07 [SOS]).. Following our results an increase incidence of reduced speed of sound occurs in asthmatic children which is attributed to asthma severity and seems to be negatively influenced even by topically applied low dose steroids. This could be attributed to a steroid induced collagen synthesis deficiency followed by a reduced bone elasticity. Further studies, especially using a longitudinal study design are required to verify these findings.

Topics: Adolescent; Adrenal Cortex Hormones; Age Factors; Androstadienes; Anti-Inflammatory Agents; Asthma; Body Height; Body Weight; Bronchodilator Agents; Budesonide; Child; Female; Fluticasone; Humans; Male; Multivariate Analysis; Sex Factors; Ultrasonography

Budesonide (BDS) is a potent corticosteroid that has important implications in the pharmacotherapy of inflammatory bowel disease, especially in the treatment of ulcerative colitis and Crohn's disease. BDS is available on the market in the form of enteric-coated preparations. However these products, similar to other available site-specific dosage forms, are not sufficiently selective to treat colonic inflammatory bowel disease. The objective of this study was to evaluate the efficacy of a new microparticulate system containing BDS, to treat experimentally induced colitis in rats. This microparticulate system consisted of BDS-containing hydrophobic cores, microencapsulated within an enteric polymer, which solubilizes at above pH 7, thus combining pH-sensitive and controlled-release properties. Colonic injury and inflammation were assessed by measuring colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring macroscopic and histological damage in colitic rats. Rats were treated orally with BDS, included in the developed system, once a day for 4 days after the induction of inflammation. A BDS suspension and BDS-containing enteric microparticles were included as control formulations in the experimental design. The administration of the new BDS delivery system significantly reduced the colon/bodyweight ratio compared with the administration of control formulations. Similarly, MPO activity and macroscopic and histological damage of the inflamed colonic segments decreased significantly when the BDS formulation was administered, compared with the results obtained after oral administration of the drug suspension. There were no significant differences, however, when the new treatment was compared with the control formulation consisting of simple enteric microparticles.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Body Weight; Budesonide; Colitis; Colon; Disease Models, Animal; Drug Compounding; Drug Delivery Systems; Inflammation; Male; Rats; Rats, Sprague-Dawley

We studied the effect of inhaled corticosteroids on the increase in bone mineral content in prepubertal children with asthma. Forty-eight asthmatic, prepubertal children receiving either inhaled beclomethasone dipropionate or budesonide were evaluated. Nine children of similar age not receiving inhaled steroids served as controls. The average age of corticosteroid-treated children was 7.8 +/- 2.4 years, and of control children, 8.4 +/- 2.1 years (NS). The average dose of inhaled corticosteroids in the treated children was 0.67 +/- 0.48 mg/m(2)/day, and they were followed over a 9-20-month period. Total bone mineral content (TBMC) was measured at baseline and after 9-20 months. A derived value for 12 months' TBMC was calculated, assuming that changes in TBMC were linear with the passage of time. The change in TBMC over a 12-month period was 264 +/- 68 mg for the corticosteroid-treated children and 330 +/- 84 mg for control children (P < 0.025). In a multiple regression analysis in which adjustments were made for the effects of age, height, and weight, the change in TBMC in corticosteroid-treated children was inversely related to the inhaled steroid dose/m(2)/day (P = 0.016). The increase in the lumbar vertebral bone mineral density in control children was also significantly greater than in the corticosteroid-treated children (P < 0.025). We conclude that inhaled steroids, at an average dose of 0.67 mg/m(2)/day, when used in the treatment of asthma reduce the acquisition of bone mineral in prepubertal children.

Topics: Absorptiometry, Photon; Administration, Inhalation; Administration, Topical; Adolescent; Age Factors; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Follow-Up Studies; Glucocorticoids; Humans; Linear Models; Lumbar Vertebrae; Male; Puberty

This investigation is part of a continuing effort to develop effective chemoprevention for carcinogenesis of the lung. The present study explores the use of aerosol administrations for this purpose. The agent selected for initial study was the synthetic glucocorticoid budesonide. This selection was based on previous work in which budesonide added to the diet was found to inhibit pulmonary adenoma formation in female A/J mice. However, high dose levels were required, i.e., of the order of 300 microg/kg, of body weight [L. W. Wattenberg and R. D. Estensen, Carcinogenesis (Lond.), 18: 2015-2017, 1997]. For aerosol administration of budesonide, a nose-only technique has been developed that entails nebulization of the compound dissolved in ethanol and subsequent stripping off of the solvent (less than 3 microl ethanol/liter of air remaining at the site of inhalation). The budesonide particles produced by the apparatus had a mass median aerodynamic diameter of less than 1 microm. An experiment has been carried out in which the inhibitory effects of aerosolized budesonide, given for 1 min six times a week, were studied. Concentrations of budesonide of 26, 81, and 148 microg/liter of air (calculated doses of 23, 72, and 126 microg/kg of body weight) were used. The aerosols were started 1 week after three oral administrations of benzo(a)pyrene (2 mg/20 g of body weight) to female A/J mice. All three doses of budesonide resulted in more than 80% inhibition of pulmonary tumor formation compared to the aerosol control and 90% or greater compared to mice not exposed to aerosol. The difference in inhibition is due to the aerosol procedure itself, which produces a reduction in tumor formation. A decrease in splenic weight (evidence of a systemic effect) occurred at all doses of budesonide. To the best of our knowledge, this is the first published effort at the use of aerosol administration to prevent neoplasia of the respiratory tract. The results of the present study show that administration of a potential chemopreventive agent by aerosol at a low dose can inhibit the occurrence of pulmonary carcinogenesis in female A/J mice.

Topics: Administration, Inhalation; Aerosols; Animals; Anticarcinogenic Agents; Benzo(a)pyrene; Body Weight; Budesonide; Carcinogens; Female; Lung Neoplasms; Mice; Mice, Inbred A; Particle Size

We evaluated serum and urinary markers of bone turnover in 14 children with asthma during inhaled budesonide and nedocromil treatments. Both the markers of formation (serum carboxy- and amino-terminal propeptides of type I procollagen and serum osteocalcin) and the markers of degradation (serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links) decreased (p < 0.05) during budesonide treatment for 6 months. During inhaled nedocromil treatment (for the following 6 months), the markers returned to the normal levels. These transient decreases in the markers of both formation and degradation of bone suggest that inhaled budesonide may slightly decrease the bone turnover rate. However, normal "coupling" between formation and degradation seemed to operate, e.g. a change in one resulted in a corresponding change in the other, so that net bone loss did not necessarily occur.

Topics: Anti-Asthmatic Agents; Asthma; Biomarkers; Body Height; Body Weight; Bone Remodeling; Budesonide; Child; Collagen; Female; Humans; Male; Nedocromil; Peptide Fragments; Pregnenediones; Procollagen; Respiratory Function Tests; Treatment Outcome

To study the effect of local or parenteral administration of the glucocorticoid budesonide in the acetic acid-induced colitis model in the rat.. Colitis was induced in an exteriorized colonic segment by administration of 4% acetic acid for 15 s. Four days later, this colonic segment with colitis was examined using a morphological scoring system, and measurements of myeloperoxidase activity and of plasma exudation into the colonic segment. The experimental colitis showed morphological similarities to human ulcerative colitis, with 3-fold increase in myeloperoxidase activity and 6-fold increase in the plasma exudation. Budesonide in different doses administered for 3 days, starting one day after acetic acid instillation, prevented the development of colitis in a dose-dependent manner. The best effect of budesonide on the morphological score was achieved after local treatment at a dose of 10(-5) M twice daily (76% reduction compared with a control colitis group) and parenteral treatment with 0.75 mg/kg (80% reduction). These doses also normalized myeloperoxidase activity and significantly reduced the plasma exudation. The systemic effects of the drug were most pronounced in the group treated with parenteral budesonide. This group showed the greatest reduction in body weight and a significant reduction of the weight of adrenal glands and spleen (as compared to controls). Thymus weight in animals treated systemically was significantly lower than in locally treated animals. In the group treated with local budesonide the weight of adrenals was reduced. However, the weights of spleen and thymus were not reduced and the reduction of the body weight was even less than in the control group.. Local treatment with budesonide at a dose of 10(-5) M (0.17 mg/kg if completely absorbed, but only 0.03 mg/kg with 15% bioavailability on colonic application) was as effective as parenteral treatment at a dose of 0.75 mg/kg in the attenuation of acetic acid-induced colitis in the rat, but resulted in minor systemic side-effects.

Topics: Acetates; Acetic Acid; Administration, Topical; Animals; Anti-Inflammatory Agents; Body Weight; Budesonide; Colitis; Dose-Response Relationship, Drug; Female; Glucocorticoids; Injections, Subcutaneous; Organ Size; Peroxidase; Pregnenediones; Rats; Rats, Sprague-Dawley

Childhood asthma generally responds well to inhaled corticosteroids within the dosage range recommended by the manufacturers, but it is sometimes necessary to use higher doses--that is, above 400 micrograms/day--a practice which has become more widespread recently. Whereas the lack of adrenal suppression in children given inhaled corticosteroids in normal doses is well documented, little is known about the effects of higher doses.. The effects on adrenal function of high dose (above 400 micrograms/day) inhaled corticosteroids were evaluated by measuring cortisol concentration in the morning and performing a short tetracosactrin test in 49 children taking budesonide (mean age 9.2 years (range 4 to 16 years) and 28 children taking beclomethasone dipropionate (10.2 years (5 to 13 years)). Twenty three non-asthmatic children (8.9 years (4.9 to 13 years)) who were under investigation for short stature served as controls for the study.. Compared with controls mean basal cortisol concentration was lower in children taking budesonide and beclomethasone dipropionate (control 401 (26.8) nmol/l, budesonide 284 (22) nmol/l, beclomethasone dipropionate 279 (23.2) nmol/l). Sixteen of the 49 children taking budesonide had subnormal basal cortisol concentrations compared with seven of the 28 taking beclomethasone dipropionate. Mean stimulated cortisol concentrations were lower in children taking inhaled corticosteroids than in controls, with no difference between those taking budesonide or beclomethasone dipropionate.. Adrenal suppression occurs in some children who are given inhaled corticosteroids in doses greater than 400 micrograms/day. It may therefore be advisable to try alternative treatments before such doses are used.

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex; Asthma; Beclomethasone; Body Height; Body Weight; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Female; Humans; Hydrocortisone; Male; Pregnenediones; Time Factors

Male rats treated with either budesonide, prednisolone, or triamcinolone acetonide in drinking water for up to 104 weeks developed slightly increased incidences of basophilic foci, and significantly increased incidences of combined hepatocellular adenomas/carcinomas as compared to controls. Based upon reduced body weight gains and survivals, the doses administered were considered to be toxic. It was concluded that the positive findings represented a class effect, and probably involved glucocorticoid receptors.

Topics: Adenoma; Administration, Topical; Animals; Anti-Inflammatory Agents; Body Weight; Budesonide; Drinking; Glucocorticoids; Liver Neoplasms, Experimental; Male; Prednisolone; Pregnenediones; Rats; Rats, Sprague-Dawley; Triamcinolone Acetonide

Topics: Animals; Body Weight; Budesonide; Cyclosporine; Diabetes Mellitus, Experimental; Glucocorticoids; Graft Survival; Injections, Intravenous; Islets of Langerhans Transplantation; Portal Vein; Pregnenediones; Rats; Rats, Inbred Lew; Rats, Inbred WF; Tacrolimus; Transplantation, Homologous

An investigation was carried out to determine whether the sensitivity of rat tracheal smooth muscle to contractile and relaxant drugs was affected by three weeks' treatment with subcutaneous budesonide before death. Budesonide treatment was associated with a lower thymus weight and a smaller gain in body weight than in control animals. There was, however, no difference in the carbachol concentration-response curves or maximum responses to carbachol of tracheal smooth muscle from control and budesonide treated rats. Isometric and isotonic recordings agreed in these respects. Glucocorticoid treatment did not increase the sensitivity of tracheal smooth muscle to the relaxant drugs terbutaline and enprofylline; if anything there was a tendency for terbutaline and enprofylline to be less potent after budesonide treatment. The data suggest that in vivo effects of glucocorticoids on airway responsiveness to bronchodilating and bronchoconstricting drugs are unlikely to be due to a direct effect on bronchial smooth muscle.

Topics: Animals; Body Weight; Budesonide; Carbachol; Culture Techniques; Glucocorticoids; Male; Muscle Contraction; Muscle, Smooth; Pregnenediones; Rats; Rats, Inbred Strains; Terbutaline; Thymus Gland; Trachea; Xanthines

16 alpha,17 alpha-Butylidenedioxy-11 beta,21-dihydroxypregna-1,4-diene-3,20- dione (budesonide) was administered subcutaneously to male and female Wistar rats at the doses 0.01, 0.1 and 5 micrograms/kg/d (10 animals/group), and 5, 20 and 80 micrograms/kg/d (15 animals/group) for 26 weeks in two separate studies. A dose-dependent decrease in body weight gain in the groups given 5, 20 and 80 micrograms/kg/d compared with the control group was noted as well as a dose-related reduction in food intake in males receiving 20 or 80 micrograms/kg/d. Increased values for packed cell volume, hemoglobin concentration and erythrocyte counts were found for both sexes at the dose levels 20 and 80 micrograms/kg/d. Also a marked decrease in the number of lymphocytes was seen for both sexes at 80 micrograms/kg/d, and for females also at 20 micrograms/kg/d. Pathological changes associated with treatment with budesonide were found in the liver--panacinar hepatocytic fine vacuolation in females receiving 80 micrograms/kg/d; cervical lymph nodes--low numbers of small lymphocytes in both males and females receiving 20 or 80 micrograms/kg/d; mesenteric lymph nodes--low numbers of small lymphocytes in females receiving 20 or 80 micrograms/kg/d; thymus--low numbers of small lymphocytes in females receiving 80 micrograms/kg/d; mammary glands--acinar hyperplasia and secretion in both sexes receiving 20 and 80 micrograms/kg/d; uterus--dilation of the lumen in females receiving 20 or 80 micrograms/kg/d. Treatment with budesonide at doses of 5 micrograms/kg/d and below was without effect upon the morphology.

Topics: Animals; Anti-Inflammatory Agents; Body Weight; Budesonide; Organ Size; Pregnenediones; Rats; Rats, Inbred Strains

16 alpha,17 alpha-Butylidenedioxy-11 beta,21-dihydroxy-pregna-1,4-diene-3,20-dione (budesonide), a newly developed glucocorticosteroid, was administered subcutaneously to pregnant rabbits at doses of 0.01, 0.06 and 0.29 mumol/kg during the organogenetic period. As a reference compound the glucocorticosteroid fluocinolone acetonide, at the dose 0.28 mumol/kg, was used. In the group given 0.06 mumol/kg 2 dams out of 15 aborted. All animals receiving 0.29 mumol/kg aborted. All dams receiving fluocinolone acetonide aborted. The food consumption was reduced in all groups given budesonide. The body weight change was dose-dependently reduced for the groups receiving budesonide. The group receiving fluocinolone acetonide also showed a negative body weight change compared with the control group. The affected litter parameters were: reduced litter and fetal weight in the groups receiving 0.01 and 0.06 mumol/kg of budesonide, indicating intrauterine growth retardation. Furthermore, the frequency of fetal abnormalities, mainly skeletal anomalies, was significantly increased in the group receiving 0.06 mumol/kg of budesonide. The anomalies seen were mostly different kinds of delayed development of the bones in the skull and at the vertebra. A direct teratogenic effect cannot be excluded but severe maternal toxic reactions may have contributed to the pregnancy outcome.

Topics: Abortion, Spontaneous; Animals; Body Weight; Budesonide; Eating; Female; Fetus; Fluocinolone Acetonide; Injections, Subcutaneous; Pregnancy; Pregnenediones; Rabbits; Teratogens