Sample records for beclomethasone

  1. Inhaled beclomethasone in pregnant asthmatic women--a systematic review. (United States)

    de Aguiar, M M; da Silva, H J; Rizzo, J Â; Leite, D F B; Silva Lima, M E P L; Sarinho, E S C


    The aim of this study was to systematically review the safety and efficacy of inhaled beclomethasone for asthma treatment in pregnant women. We performed a systematic review in Medline, LILACS and SciELO electronic databases in December 2012. A total of 3433 articles were found by using the keywords asthma, pregnancy and beclomethasone. Among these, 1666 were from Medline, via PubMed, and 1767 were from LILACS and SciELO. Nine of these articles were selected. Only one paper suggested an increased foetal risk for congenital malformations, and one other for offspring endocrine and metabolic disturbances. Data are mostly reassuring, supporting the use of glucocorticoid inhalants during pregnancy, and we found no evidence of inferiority in relation to efficacy and safety of beclomethasone compared to other drugs used in pregnant asthmatic women.

  2. Adrenal function in children with bronchial asthma treated with beclomethasone dipropionate or budesonide

    DEFF Research Database (Denmark)

    Bisgaard, H; Damkjaer Nielsen, M; Andersen, B;


    The effect of inhaled beclomethasone dipropionate and budesonide on the adrenal function was studied in 30 children (aged 7 to 15 years) with mild bronchial asthma. The trial was designed as a prospective double-blind parallel study of the effect of stepwise increase of either beclomethasone...... difference was found between the two topical steroids (probability value 5.3%), and yet the suppression was apparent in the group of children treated with beclomethasone dipropionate but not in the group of children treated with budesonide. Further studies are desirable in order to ascertain whether...

  3. Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

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    Gopala Krishna Murthy Talasila


    Full Text Available Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

  4. Long-term beclomethasone dipropionate aerosol therapy in juvenile asthma. (United States)

    Francis, R S


    Following a short-term clinical trial reported elsewhere, beclomethasone dipropionate aerosol has been given to 15 children with asthma for between 2 1/2 and 3 years except for a short placebo period after the first year. Month-by-month records of wheezing, peak flow rate, and other treatments used are presented for the first 17 months, adrenocortical function tests are reported for the first 2 years, and growth is recorded for 2 1/2-3 years. The short-term clinical benefits of the treatment are confirmed in the longer term, adrenocortical function appears to be unchanged, and growth proceeds along expected lines. The main disadvantage seems to be worsening of eczema and allergic rhinitis in those children who have ceased using corticotrophin or oral steroids for the control of asthma. It is concluded that in the long term beclomethasone dipropionate aerosol provides safe and effective day-to-day control of asthma in children, although occasional recourse to systemic steroid therapy cannot be avoided. Oral candidasis has not been a clinical problem.

  5. Beclomethasone dipropionate enema in ulcerative colitis: Is it safe? (United States)

    Luboshitzky, Rafael; Rachelis, Zoia; Nussensone, Elchanan; Ishay, Avraham


    Objective: To evaluate the pituitary-adrenal axis (PA axis) reserve in patients with ulcerative colitis (UC) treated with steroid enemas, we performed 1mug ACTH test.Methods: Patients with UC (n=8) given beclomethasone dipropionate enema (Betnesol) for 4 weeks. Fasting serum cortisol and the response at 30 and 60 minutes following an IV 1mug ACTH injection were determined after 2 weeks of Betnesol enemas. Patients were retested, one month after discontinuation of enemas.Results: Fasting and peak cortisol responses to ACTH were suppressed in six patients. Additional patient had suppressed fasting cortisol and another patient had blunted response to ACTH. One month off Betnesol enema, basal and peak cortisol response to ACTH were normal in all but one patient.Conclusion: Betnesol enemas are associated with severe suppression of the PA axis in almost all patients. Caution is required in patients with UC after withdrawal of rectal steroids as adrenal insufficiency can occur.

  6. Pharmacokinetics of inhaled monodisperse beclomethasone as a function of particle size

    NARCIS (Netherlands)

    J.E. Esposito-Festen; P. Zanen (Pieter); H.A.W.M. Tiddens (Harm); J.-W.J. Lammers (Jan-Willem)


    textabstractAims: For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP)

  7. Solubilization of beclomethasone dipropionate in sterically stabilized phospholipid nanomicelles (SSMs: physicochemical and in vitro evaluations

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    Peh KK


    Full Text Available Mohanad Naji Sahib, Shaymaa Abdalwahed Abdulameer, Yusrida Darwis, Kok Khiang Peh, Yvonne Tze Fung TanSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, MalaysiaBackground: The local treatment of lung disorders such as asthma and chronic obstructive pulmonary disease via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration. This is because direct deposition of a drug at the diseased site increases local drug concentrations, which improves the pulmonary receptor occupancy and reduces the overall dose required, therefore reducing the side effects that result from high drug doses. From a clinical point of view, although jet nebulizers have been used for aerosol delivery of water-soluble compounds and micronized suspensions, their use with hydrophobic drugs has been inadequate.Aim: To evaluate the feasibility of sterically stabilized phospholipid nanomicelles (SSMs loaded with beclomethasone dipropionate (BDP as a carrier for pulmonary delivery.Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 5000 polymeric micelles containing BDP (BDP-SSMs were prepared by the coprecipitation and reconstitution method, and the physicochemical and in vitro characteristics of BDP-SSMs were investigated.Results: BDP-SSMs were successfully prepared with a content uniformity and reproducibility suitable for pulmonary administration. The maximum solubility of BDP in SSMs was approximately 1300 times its actual solubility. The particle size and zeta potential of BDP-SSMs were 19.89 ± 0.67 nm and -28.03 ± 2.05 mV, respectively. The SSMs system slowed down the release of BDP and all of the aerodynamic values of the aerosolized rehydrated BDP-SSMs were not only acceptable but indicated a significant level of deposition in the lungs.Conclusion: The SSM system might be an effective way of improving the therapeutic index of nebulized, poorly soluble corticosteroids

  8. Prophylactic Effects of Lidocaine or Beclomethasone Spray on Post-Operative sore Throat and Cough after Orotracheal Intubation

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    Nadia Banihashem


    Full Text Available Introduction: Post-operative sore throat and cough are common complications of endotracheal intubation. These conditions may be very distressing for the patient and may lead to unpleasant memories. This study was performed in order to determine whether beclomethasone and lidocaine spray could reduce the frequency of post-operative sore throat and hoarseness after tracheal extubation.  Materials and Methods: Ninety women (18–60 years of age with an American Society of Anesthesiologists (ASA physical status I or II and undergoing elective mastoidectomy were randomized into three groups of 30 patients. The endotracheal tubes in each group were sprayed with 50% beclomethasone, 10% lidocaine hydrochloride, or normal saline (control group before endotracheal intubation. Patients were examined for sore throat (none, mild, moderate, or severe, cough, and hoarseness at 1 and 24 h after extubation.  Results: There was a significantly lower incidence and severity of post-operative sore throat in the beclomethasone group than the lidocaine and control groups (P

  9. Noninterventional open-label trial investigating the efficacy and safety of ectoine containing nasal spray in comparison with beclomethasone nasal spray in patients with allergic rhinitis. (United States)

    Sonnemann, Uwe; Möller, Marcus; Bilstein, Andreas


    Objectives. The current study aimed to compare the efficacy and safety of a classical anti-inflammatory beclomethasone nasal spray in comparison to a physic-chemical stabilizing ectoine containing nasal spray in the treatment of allergic rhinitis. Design and Methods. This was a noninterventional, open-label, observational trial investigating the effects of beclomethasone or ectoine nasal spray on nasal symptoms and quality of life. Over a period of 14 days, patients were asked to daily document their symptoms. Efficacy and tolerability were assessed by both physicians and patients. Results. Both treatments resulted in a significant decrease of TNSS values. An equivalence test could not confirm the noninferiority of ectoine treatment in comparison with beclomethasone treatment. Although clear symptom reduction was achieved with the ectoine products, the efficacy judgment showed possible advantages for the beclomethasone group. Importantly, tolerability results were comparably good in both groups, and a very low number of adverse events supported this observation. Both treatments resulted in a clear improvement in the quality of life as assessed by a questionnaire answered at the beginning and at the end of the trial. Conclusion. Taken together, it was shown that allergic rhinitis can be safely and successfully treated with beclomethasone and also efficacy and safety were shown for ectoine nasal spray.

  10. Noninterventional Open-Label Trial Investigating the Efficacy and Safety of Ectoine Containing Nasal Spray in Comparison with Beclomethasone Nasal Spray in Patients with Allergic Rhinitis

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    Uwe Sonnemann


    Full Text Available Objectives. The current study aimed to compare the efficacy and safety of a classical anti-inflammatory beclomethasone nasal spray in comparison to a physic-chemical stabilizing ectoine containing nasal spray in the treatment of allergic rhinitis. Design and Methods. This was a noninterventional, open-label, observational trial investigating the effects of beclomethasone or ectoine nasal spray on nasal symptoms and quality of life. Over a period of 14 days, patients were asked to daily document their symptoms. Efficacy and tolerability were assessed by both physicians and patients. Results. Both treatments resulted in a significant decrease of TNSS values. An equivalence test could not confirm the noninferiority of ectoine treatment in comparison with beclomethasone treatment. Although clear symptom reduction was achieved with the ectoine products, the efficacy judgment showed possible advantages for the beclomethasone group. Importantly, tolerability results were comparably good in both groups, and a very low number of adverse events supported this observation. Both treatments resulted in a clear improvement in the quality of life as assessed by a questionnaire answered at the beginning and at the end of the trial. Conclusion. Taken together, it was shown that allergic rhinitis can be safely and successfully treated with beclomethasone and also efficacy and safety were shown for ectoine nasal spray.

  11. Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients

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    Tzani P


    Full Text Available Panagiota Tzani1, Ernesto Crisafulli2, Gabriele Nicolini3, Marina Aiello1, Alfredo Chetta1, Enrico Maria Clini2, Dario Olivieri1 1Department of Clinical Sciences, University of Parma, Parma, Italy; 2Department of Oncology Haematology and Pulmonary Diseases, University of Modena and Ospedale Villa Pineta, Pavullo, Modena, Italy; 3Medical Affairs Department, Chiesi Farmaceutici SpA, Parma, Italy Background: Chronic obstructive pulmonary disease (COPD is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation. Objectives: The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S combination treatment was the active control. Methods: COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity ≥120% of predicted were randomized to a double-blind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 µg/day or FP/S 500/100 µg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index. Results: Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S. Conclusion: BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation. Keywords: small airways, chronic obstructive pulmonary disease, airflow obstruction 

  12. Humidity affects the morphology of particles emitted from beclomethasone dipropionate pressurized metered dose inhalers. (United States)

    Ivey, James W; Bhambri, Pallavi; Church, Tanya K; Lewis, David A; McDermott, Mark T; Elbayomy, Shereen; Finlay, Warren H; Vehring, Reinhard


    The effects of propellant type, cosolvent content, and air humidity on the morphology and solid phase of the particles produced from solution pressurized metered dose inhalers containing the corticosteroid beclomethasone dipropionate were investigated. The active ingredient was dissolved in the HFA propellants 134a and 227ea with varying levels of the cosolvent ethanol and filled into pressurized metered dose inhalers. Inhalers were actuated into an evaporation chamber under controlled temperature and humidity conditions and sampled using a single nozzle, single stage inertial impactor. Particle morphology was assessed qualitatively using field emission scanning electron microscopy and focused ion beam-helium ion microscopy. Drug solid phase was assessed using Raman microscopy. The relative humidity of the air during inhaler actuation was found to have a strong effect on the particle morphology, with solid spheroidal particles produced in dry air and highly porous particles produced at higher humidity levels. Air humidification was found to have no effect on the solid phase of the drug particles, which was predominantly amorphous for all tested formulations. A critical level of air relative humidity was required to generate porous particles for each tested formulation. This critical relative humidity was found to depend on the amount of ethanol used in the inhaler, but not on the type of propellant utilized. The results indicate that under the right circumstances water vapor saturation followed by nucleated water condensation or ice deposition occurs during particle formation from evaporating propellant-cosolvent-BDP droplets. This finding reveals the importance of condensed water or ice as a templating agent for porosity when particle formation occurs at saturated conditions, with possible implications on the pharmacokinetics of solution pMDIs and potential applications in particle engineering for drug delivery.

  13. Monitoring the initial pulmonary absorption of two different beclomethasone dipropionate aerosols employing a human lung reperfusion model

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    Fritz Peter


    Full Text Available Abstract Background The pulmonary residence time of inhaled glucocorticoids as well as their rate and extend of absorption into systemic circulation are important facets of their efficacy-safety profile. We evaluated a novel approach to elucidate the pulmonary absorption of an inhaled glucocorticoid. Our objective was to monitor and compare the combined process of drug particle dissolution, pro-drug activation and time course of initial distribution from human lung tissue into plasma for two different glucocorticoid formulations. Methods We chose beclomethasone dipropionate (BDP delivered by two different commercially available HFA-propelled metered dose inhalers (Sanasthmax®/Becloforte™ and Ventolair®/Qvar™. Initially we developed a simple dialysis model to assess the transfer of BDP and its active metabolite from human lung homogenate into human plasma. In a novel experimental setting we then administered the aerosols into the bronchus of an extracorporally ventilated and reperfused human lung lobe and monitored the concentrations of BDP and its metabolites in the reperfusion fluid. Results Unexpectedly, we observed differences between the two aerosol formulations Sanasthmax®/Becloforte™ and Ventolair®/Qvar™ in both the dialysis as well as in the human reperfusion model. The HFA-BDP formulated as Ventolair®/Qvar™ displayed a more rapid release from lung tissue compared to Sanasthmax®/Becloforte™. We succeeded to explain and illustrate the observed differences between the two aerosols with their unique particle topology and divergent dissolution behaviour in human bronchial fluid. Conclusion We conclude that though the ultrafine particles of Ventolair®/Qvar™ are beneficial for high lung deposition, they also yield a less desired more rapid systemic drug delivery. While the differences between Sanasthmax®/Becloforte™ and Ventolair®/Qvar™ were obvious in both the dialysis and lung perfusion experiments, the latter

  14. Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children

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    Cutrera Renato


    Full Text Available Abstract Background Few data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS in pre-school children with wheezing exacerbations. Methods To compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP, plus nebulized 2500 μg prn salbutamol (BDP group, versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group, a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode. Results The percentage of symptom-free days (SFDs was significantly higher in the BDP group (54.7% than in the placebo group (40.5%; p = 0.012, with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%, the difference reaching statistical significance at day 6 (12.3%; p = 0.035. Cough score was also reduced in the BDP group (0.11 as compared with the placebo group (0.39; p = 0.048, the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047. The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively, but the difference was not significant (p = 0.366. There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma. Conclusions A 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children. Trial Registration (NCT00497523

  15. Comparison of beclomethasone dipropionate (2 and 3 mg) and prednisolone sodium phosphate enemas (30 mg) in the treatment of ulcerative proctitis. An adrenocortical approach. (United States)

    Mulder, C J; Endert, E; van der Heide, H; Houthoff, H J; Wiersinga, W; Wiltink, E H; Tytgat, G N


    Twenty-three patients with attacks of distal ulcerative colitis were treated randomly with either 2 or 3 mg of topically administered beclomethasone dipropionate (BDP) or 30 mg of prednisolone sodium phosphate (PP). The effect of the steroid enemas on adrenocortical function was assessed by ACTH tests, which were performed before and after treatment. Endoscopic, clinical and histological scores were comparable in the three treatment groups in this pilot trial. Fasting cortisol in the PP group decreased significantly from 0.47 +/- 0.12 mumol/l before to 0.22 +/- 0.14 mumol/l (P less than 0.05) after therapy; in the BDP group no significant changes were found. Urinary cortisol excretion in the PP group was not detectable after therapy; in the BDP group no changes were found. It is concluded that in the topical treatment of ulcerative colitis, BDP may be preferable to PP because it exerts a promising anti-inflammatory action without affecting adrenocortical function.

  16. Comparison of clinical effects of beclomethasone dipropionate & budesonide in treatment of children with mild persistent asthma: A double-blind, randomized, controlled study (United States)

    Singh, Anju; Nandan, Devki; Dewan, Vivek; Sankar, Jhuma


    Background & objectives: Various inhaled corticosteroids (ICSs) are available to control the symptoms of asthma. Although beclomethasone dipropionate (BDP) and budesonide (BUD) are one of the oldest ICSs, their wide availability and low cost make them attractive options in developing countries. Due to lack of consensus on which of the two drugs is better for controlling mild persistent asthma, we undertook this study to compare the efficacy of these two drugs by measuring the change in percentage predicted forced expiratory volume in one second (FEV1) from baseline in children with mild persistent asthma. Methods: A double-blind, randomized, parallel group study was conducted in children 7-15 yr of age with newly diagnosed asthma. Of the 85 cases of mild persistent asthma, 42 received BUD while 43 received BDP at a dose of 400 µg/day using pressurized metered-dose inhaler with valved spacer for two months. The outcomes measured were change in FEV1, symptom scores and side effects. Results: There was a significant (P management of children with mild persistent asthma. [CTRI No: CTRI/2013/03/003495]. PMID:27934805

  17. Development and validation of simultaneous spectrophotometric and TLC-spectrodensitometric methods for determination of beclomethasone dipropionate and salbutamol in combined dosage form (United States)

    Samir, Ahmed; Lotfy, Hayam M.; Salem, Hesham; Abdelkawy, Mohammed


    Spectrophotometric and TLC-spectrodensitometric methods were developed and validated for the simultaneous determination of beclomethasone dipropionate (BEC) and salbutamol (SAL). The spectrophotometric methods include dual wavelength, ratio difference, constant center coupled with a novel method namely, spectrum subtraction and mean centering with mean percentage recoveries and RSD 99.72 ± 1.07 and 99.70 ± 1.12, 100.25 ± 1.12 and 99.89 ± 1.12, 99.66 ± 1.85 and 99.19 ± 1.32, 100.74 ± 1.26 and 101.06 ± 0.90 for BEC and SAL respectively. The TLC-spectrodensitometric method was based on separation of both drugs on TLC aluminum plates of silica gel 60 F254, using benzene: methanol: triethylamine (10:1.5:0.5 v/v/v) as a mobile phase, followed by densitometric measurements of their bands at 230 nm. The mean percentage recoveries and RSD were 99.07 ± 1.25 and 101.35 ± 1.50 for BEC and SAL respectively. The proposed methods were validated according to ICH guidelines and were applied for the simultaneous analysis of the cited drugs in synthetic mixtures and pharmaceutical preparation. The methods were found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of BEC and SAL in their pharmaceutical formulation with no need for prior separation. The results obtained were statistically compared to each other and to that of the reported HPLC method. The statistical comparison showed that there is no significant difference regarding both accuracy and precision.

  18. Towards the bioequivalence of pressurised metered dose inhalers 1: design and characterisation of aerodynamically equivalent beclomethasone dipropionate inhalers with and without glycerol as a non-volatile excipient. (United States)

    Lewis, D A; Young, P M; Buttini, F; Church, T; Colombo, P; Forbes, B; Haghi, M; Johnson, R; O'Shea, H; Salama, R; Traini, D


    A series of semi-empirical equations were utilised to design two solution based pressurised metered dose inhaler (pMDI) formulations, with equivalent aerosol performance but different physicochemical properties. Both inhaler formulations contained the drug, beclomethasone dipropionate (BDP), a volatile mixture of ethanol co-solvent and propellant (hydrofluoroalkane-HFA). However, one formulation was designed such that the emitted aerosol particles contained BDP and glycerol, a common inhalation particle modifying excipient, in a 1:1 mass ratio. By modifying the formulation parameters, including actuator orifice, HFA and metering volumes, it was possible to produce two formulations (glycerol-free and glycerol-containing) which had identical mass median aerodynamic diameters (2.4μm±0.1 and 2.5μm±0.2), fine particle dose (⩽5μm; 66μg±6 and 68μg±2) and fine particle fractions (28%±2% and 30%±1%), respectively. These observations demonstrate that it is possible to engineer formulations that generate aerosol particles with very different compositions to have similar emitted dose and in vitro deposition profiles, thus making them equivalent in terms of aerosol performance. Analysis of the physicochemical properties of each formulation identified significant differences in terms of morphology, thermal properties and drug dissolution of emitted particles. The particles produced from both formulations were amorphous; however, the formulation containing glycerol generated particles with a porous structure, while the glycerol-free formulation generated particles with a primarily spherical morphology. Furthermore, the glycerol-containing particles had a significantly lower dissolution rate (7.8%±2.1%, over 180min) compared to the glycerol-free particles (58.0%±2.9%, over 60min) when measured using a Franz diffusion cell. It is hypothesised that the presence of glycerol in the emitted aerosol particles altered solubility and drug transport, which may have

  19. Long-term safety of Mometasone Furoate administered via a dry powder inhaler in children: Results of an open-label study comparing Mometasone Furoate with Beclomethasone Dipropionate in children with persistent asthma

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    Corren Jonathan


    Full Text Available Abstract Background To assess the long-term pediatric safety of 2 doses of mometasone furoate administered via a dry powder inhaler (MF-DPI for mild-to-moderate persistent asthma and compare them with that of beclomethasone dipropionate administered via a metered dose inhaler (BDP-MDI in the treatment of persistent asthma. Both MF-DPI doses tested are twice the approved pediatric dosage of 100 μg once-daily (QD for children aged 4–11 years. Methods Children (N = 233 aged 4–11 years were randomized to 52 weeks of treatment with MF-DPI 200 μg QD AM, MF-DPI 100 μg twice daily (BID, or BDP-MDI 168 μg BID. Patients had used inhaled corticosteroids (ICSs daily for ≥ 30 days before the screening visit and were on stable ICS doses for ≥ 2 weeks before screening. The primary safety variable was the incidence of adverse events. Secondary safety variables were laboratory tests (including cortisol concentrations, vital signs, and physical examination. Results The incidence of adverse events was similar in all 3 treatment groups. The most frequently reported adverse event was upper respiratory tract infection, reported by 47%–49% of the MF-DPI-treated patients and 51% of the BPD-treated patients. Most adverse events were considered unrelated to study drug. The most frequently reported related adverse events were headache (MF-DPI 200 μg QD AM, 8%; MF-DPI 100 μg BID, 4%; BDP-MDI 168 μg BID, 2% and oral candidiasis (4% in each treatment group. No clinically relevant changes in laboratory values, including plasma cortisol, vital signs, or physical examinations were noted in any treatment group. Conclusion Both MF-DPI doses were well tolerated, with no unusual or unexpected adverse events or safety concerns, and had a similar adverse event profile to that of BDP-MDI 168 μg BID.

  20. Efeitos da inalação de beclometasona e furosemida sobre a função pulmonar e índice de oxigenação de recém-nascidos prematuros Efectos de la inhalación de beclometasona y furosemida sobre la función pulmonar e índice de oxigenación de recién nacidos prematuros Inhalation effects of beclomethasone and furosemide on pulmonary function and oxygenation index of preterm newborns

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    Leila Simone Foerster


    Full Text Available O objetivo deste estudo foi avaliar a função pulmonar e o índice de oxigenação de recém-nascidos pré-termo submetidos à inalação endotraqueal de beclometasona e furosemida. Foram avaliados 30 recém-nascidos pré-termo com idade gestacional El objetivo de este estudio fue evaluar la función pulmonar e índice de oxigenación de recién nacidos de pre-término sometidos a la inhalación endotraqueal de beclometasona y furosemida. Fueron evaluados 30 recién nacidos de pre-término con edad gestacional The objective of this study was to evaluate lung function and oxygenation index of preterm infants undergoing endotracheal inhaling of beclomethasone and furosemide. We studied 30 newborn preterms with gestational age <36 weeks, undergoing conventional mechanical ventilation for at least 12 hours. Three sequential inhalations with their medications were executed with an interval of three hours between each. We collected samples of arterial blood for gas analysis, and after endotracheal aspiration, the measurement of respiratory variables was performed in two stages, two hours before and after the last inhalation. Dynamic compliance and the oxygenation index showed no statistically significant difference between before and after the medication, however, the airway resistance group demonstrated a reduction in beclomethasone between the moments before and after the intervention (p=0.03. These results cannot imply that inhaled beclomethasone and furosemide exerted significant influence on lung function and oxygenation in the newborn infants studied.

  1. Avaliação da eficácia clínica, aceitabilidade e preferência de dois sistemas inalatórios de beclometasona no tratamento da asma: Pulvinal® versus Aeroliser® Acceptability, preference, tolerance and clinical efficacy of beclomethasone delivered by two inhalation devices in chronic asthma patients: Clenil pulvinal® versus Miflasona Aerolizer®

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    Jussara Fiterman


    could increase treatment compliance. OBJECTIVE: To compare the acceptability of and preference for two inhalation devices (Pulvinal and Aerolizer, as well as to evaluate the efficacy of and tolerance for beclomethasone dipropionate when delivered by these two systems. METHOD: A multicenter, randomized, crossover parallel study was carried out involving 83 patients with stable asthma. Patients received 500-1000 mg/day of beclomethasone dipropionate. After a 2-week run in, the patients were randomized to begin a 4-week crossover treatment period with equivalent doses of Clenil Pulvinal (CP or Miflasona Aerolizer (MA. RESULTS: Both groups showed improvement in dyspnea and FEV1, and acceptability was considered good or excellent in both groups. Of the patients studied, 50.6% preferred CP, and 39% preferred MA. In their future treatment regimes, 54.5% would choose the CP and 37.7% the MA. CONCLUSION: Clinical efficacy and acceptability were comparable between CP and MA.

  2. Adrenal function in children with bronchial asthma treated with beclomethasone dipropionate or budesonide

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    Bisgaard, H; Damkjaer Nielsen, M; Andersen, B;


    dipropionate or budesonide from 200 micrograms through 400 micrograms, to 800 micrograms daily in three consecutive periods of 4 weeks. At the end of each period, the adrenal stress response was evaluated by measurements of serum cortisol and androstenedione during a short adrenocorticotropic hormone test....... The unstimulated diurnal production of glucocorticosteroids was assessed by measurements of free cortisol in 24-hour urine samples. Free cortisol in urine was found a valid measure of the total diurnal excretion of cortisol metabolites, since it exhibited a good correlation to the fractional cortisol metabolites...

  3. Pharmacokinetic Comparison of Inhaled Fixed Combination vs. the Free Combination of Beclomethasone and Formoterol pMDIs in Asthmatic Children

    DEFF Research Database (Denmark)

    Chawes, Bl; Piccinno, A; Kreiner-Møller, Eskil;


    -way crossover single dose study. Blood was collected pre-dose up to 8h post-dose for pharmacokinetic evaluation (AUC(0-t) , AUC(0-∞) , AUC(0-0.5h) , C(max) , t(max) , t(1/2) ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow...... and adverse events were monitored. RESULTS: 20 subjects were evaluable. The systemic exposure of B17MP and Formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0-t) (hours(2) pg/mL) ratio Test/Reference [90% CI], 0.81 [0.697-0.948] and Formoterol AUC(0-t) (hours(2) pg....../mL) ratio Test/Reference 0.97 [0.85-1.10]. All pharmacokinetic and pharmacodynamic endpoints showed non-superiority in favour of the Test drug. One adverse event (vertigo) occurred but was not considered treatment-related. CONCLUSION: BDP and Formoterol pharmacokinetic and pharmacodynamic effects are non...

  4. A comparison of the effects of sodium cromoglycate and beclomethasone dipropionate on pulmonary function and bronchial hyperreactivity in subjects with asthma

    DEFF Research Database (Denmark)

    Svendsen, U G; Frølund, L; Madsen, F;


    After a run-in period of 2 weeks, receiving a regimen of inhaled beta 2-agonists and/or theophyllines, 38 atopic patients with asthma with perennial symptoms were randomly allocated to receive an 8-week treatment of additional inhalation treatment with either sodium cromoglycate (SCG), 2 mg four...

  5. Determination of clobetasol, beclomethasone and clobetasol propionate in cosmetics by liquid chromatography-tandem mass spectrometry%液相色谱-串联质谱法测定化妆品中的氯倍他索、倍氯米松和氯倍他索丙酸酯

    Institute of Scientific and Technical Information of China (English)

    李海玉; 陈云霞; 马强; 白桦; 张庆


    目的 建立化妆品中氯倍他索、倍氯米松和氯倍他索丙酸酯3种糖皮质激素的液相色谱-串联质谱测定方法.方法 水剂类、膏霜类化妆品样品用甲醇超声提取,提取液经Oasis HLB固相萃取柱净化,洗脱液以Waters XBridge C18色谱柱(150 mm×2.1 mm,3.5 μm)进行分离,电喷雾离子化,串联四极杆质谱多反应监测模式进行检测,外标法定量.结果 3种糖皮质激素在1 ng/ml~100 ng/ml时线性关系良好.3种糖皮质激素的平均加标回收率为80.5%~ 104.5%,相对标准偏差为1.45%~9.86%,定量限均为0.1 μg,/g.结论 该方法快速简便、灵敏可靠、分析时间短,可满足实际样品的检测需要.

  6. Clinical results obtained with a combination of an anti-inflammatory steroid, an antibacterial agent and an antifungal in dermatological outpatient practice. (United States)

    Pazzaglia, A


    Forty outpatients with skin diseases were treated with an extempore combination of three creams, the respective bases of which were beclomethasone dipropionate, sodium fusidate and ketoconazole. Positive results were obtained in 97.5% of the cases with good relief of symptoms and excellent local tolerance in all cases treated.

  7. 11.3.Upper respiratory tract disease and bronchial asthma

    Institute of Scientific and Technical Information of China (English)


    920096 A clinical trial of treating asthma ofmoderate severity with beclomethason dip-ropionate aerosol.SHEN Xun (沈勋),et al.DeptPulmon Med,Zhongshan Hosp,Shanghai MedUniv,200032.Chin J Intern Med 1991; 30 (9):536-538.In order to investigate the efficacy of steroidinhalation in treating asthma of moderate sever-

  8. Use of a combination of an anti-inflammatory corticosteroid, an antibacterial agent and an antifungal in the local post-operative treatment of cutaneo-mucosal diseases following cryosurgery. (United States)

    Gini, M


    Forty-two patients undergoing cryosurgery for skin diseases were treated by means of the simultaneous application of three creams, the respective bases of which were beclomethasone dipropionate, sodium fusidate and ketoconazole. The treatment produced excellent results, preventing bacterial and/or mycotic superinfections and relieving the edema and erythema caused by the operation in 97.6% of cases. Local tolerance was optimal in all cases; no adverse reactions of any kind being reported.

  9. Pharmacology of Nasal Medications: An Update


    Martin, G. F.


    The author of this article reviews the pharmacology of nasal medication, focusing on the indications and side-effects. The newer group of non-sedating antihistamines proves to be a useful supplement to disodium cromoglycate and the traditional antihistamines in the treatment of allergic rhinitis. The topical steroids (flunisolide and beclomethasone dipropionate) did not produce a significant incidence of adrenal suppression, mucosal atrophy, or nasal candidiasis. The anticholinergic ipatropiu...

  10. Inhaled corticosteroids for abnormal pulmonary function in children with a history of Chronic Lung Disease of Infancy: study protocol [ISRCTN55153521

    Directory of Open Access Journals (Sweden)

    Sauve Reginald


    Full Text Available Abstract Background There is considerable evidence from the literature that children with chronic lung disease of infancy (CLD have abnormal pulmonary function in childhood and this could have an impact on their life quality and overall health. There are similarities between CLD and asthma, and corticosteroids are the mainstay treatment for asthma. Many physicians use inhaled corticosteroids in children with CLD with no evidence. Therefore we wish to conduct a randomized double-blinded placebo controlled trial to test for the role of inhaled corticosteroids in children aged from3 to 9 years with a history of CLD. Our primary hypothesis will be that inhaled corticosteroids are beneficial in children with CLD. Methods Our primary hypothesis is that using inhaled steroids; Beclomethasone Dipropionate (QVAR 100 mcg 2 puffs 2 times a day for 6 weeks will improve the respiratory system resistance and the quality of life in children with CLD. Discussion We propose that Beclomethasone Dipropionate (QVAR will affect the pulmonary function after 6 weeks of treatment. In summary we think that our study will highlight knowledge on whether the use of inhaled steroids is clinically effective for CLD.

  11. Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD

    Directory of Open Access Journals (Sweden)

    Postma DS


    Full Text Available Dirkje S Postma,1 Nicolas Roche,2 Gene Colice,3 Elliot Israel,4 Richard J Martin,5 Willem MC van Aalderen,6 Jonathan Grigg,7 Anne Burden,8 Elizabeth V Hillyer,8 Julie von Ziegenweidt,8 Gokul Gopalan,9 David Price8,10 1University of Groningen, Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 2Respiratory and Intensive Care Medicine, Cochin Hospital Group, APHP, Paris-Descartes University (EA2511, Paris, France; 3Pulmonary, Critical Care and Respiratory Services, Washington Hospital Center and George Washington University School of Medicine, Washington DC, USA; 4Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; 5Department of Medicine, National Jewish Health, Denver, CO, USA; 6Dept of Pediatric Respiratory Medicine and Allergy, Emma Children's Hospital AMC, Amsterdam, the Netherlands; 7Blizard Institute, Queen Mary University London, London, UK; 8Research in Real Life, Ltd, Cambridge, UK; 9Respiratory, Global Scientific Affairs, Teva Pharmaceuticals, Frazer, PA, USA; 10Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK Purpose: Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD, which is currently treated with inhaled corticosteroids (ICS and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD grades 2–4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone and larger-particle ICS (fluticasone in primary care patients with COPD. Patients and methods: Smokers and ex-smokers with COPD ≥40 years old initiating or stepping-up their dose of extrafine beclomethasone or fluticasone were matched 1:1 for demographic characteristics, index prescription year, concomitant therapies, and disease

  12. Hidrofluoralcano como propelente dos aerossóis pressurizados de dose medida: histórico, deposição pulmonar, farmacocinética, eficácia e segurança Hydrofluoroalkane as a propellant for pressurized metered-dose inhalers: history, pulmonary deposition, pharmacokinetics, efficacy and safety

    Directory of Open Access Journals (Sweden)

    Cássio C. Ibiapina


    Full Text Available OBJETIVO: Rever a literatura sobre o hidrofluoralcano como propelente dos inaladores de dose medida contendo medicamentos empregados na asma. FONTES DOS DADOS: O levantamento bibliográfico foi realizado em bancos de dados eletrônicos - MEDLINE, MDConsult, HighWire, Medscape e LILACS - e por pesquisa direta - referentes aos últimos 15 anos -, utilizando-se as seguintes palavras-chaves: hidrofluoralcano, asma e infância. SÍNTESE DOS DADOS: Foram selecionados 43 artigos originais abordando a questão da substituição do clorofluorcarbono pelo hidrofluoralcano. Este gás mostrou-se como uma alternativa de propelente segura, com deposição pulmonar de 50 a 60% e eficácia significativa quando comparado com placebo (p OBJECTIVE: To review the literature about hydrofluoroalkane as a propellent of pressurized metered-dose inhalers containing anti-asthma drugs. SOURCES OF DATA: Bibliographic search in electronic databases (MEDLINE, MDConsult, HighWire, Medscape and LILACS and direct search referring to the past 15 years, using the key words hydrofluoroalkane, asthma and childhood were carried out. SUMMARY OF THE FINDINGS: 43 original articles on the replacement of clorofluorcarbon by hydrofluoralkane were selected. Hydrofluoralkane showed to be a safe propellent, with pulmonary deposition ranging from 50 to 60%, and to have significant efficacy, when compared with placebo (p < 0.003 in controlled clinical trials. Most works using hydrofluoralkane included beclomethasone diproprionate. Approximate annual cost of a treatment with beclomethasone diproprionate/hydrofluoralkane was lower than with beclomethasone diproprionate/clorofluorcarbon. Some studies assessed salbutamol, fluticasone, flunisolide and the association fluticasone-salmeterol, with hydrofluoralkane as propellent in pressurized metered-dose inhalers. CONCLUSIONS: Efficacy and safety of hydrofluoralkane as propellent of bronchodilators and inhaled corticosteroids in adults was evidenced

  13. Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux

    Energy Technology Data Exchange (ETDEWEB)

    Crowe, Andrew, E-mail:; Tan, Ai May


    There is concern that P-glycoprotein mediated efflux contributes to steroid resistance. Therefore, this study examined bidirectional corticosteroid transport and induction capabilities for P-glycoprotein (P-gp) to understand which of the systemic and inhaled corticosteroids interacted with P-gp to the greatest extent. Hydrocortisone, prednisolone, prednisone, methylprednisolone, and dexamethasone represented systemically active drugs, while fluticasone propionate, beclomethasone dipropionate, ciclesonide and budesonide represented inhaled corticosteroids. Aldosterone and fludrocortisone represented mineralocorticoids. All drugs were detected using individually optimised HPLC protocols. Transport studies were conducted through Caco-2 monolayers. Hydrocortisone and aldosterone had efflux ratios below 1.5, while prednisone showed a P-gp mediated efflux ratio of only 1.8 compared to its active drug, prednisolone, with an efflux ratio of 4.5. Dexamethasone and beclomethasone had efflux ratios of 2.1 and 3.3 respectively, while this increased to 5.1 for methylprednisolone. Fluticasone showed an efflux ratio of 2.3. Protein expression studies suggested that all of the inhaled corticosteroids were able to induce P-gp expression, from 1.6 to 2 times control levels. Most of the systemic corticosteroids had higher passive permeability (> 20 × 10{sup −6} cm/s) compared to the inhaled corticosteroids (> 5 × 10{sup −6} cm/s), except for budesonide, with permeability similar to the systemic corticosteroids. Inhaled corticosteroids are not transported by P-gp to the same extent as systemic corticosteroids. However, they are able to induce P-gp production. Thus, inhaled corticosteroids may have greater interactions with other P-gp substrates, but P-gp itself is less likely to influence resistance to the drugs. -- Highlights: ► Inhaled corticosteroids are only weak substrates for P-gp, including budesonide. ► Inhaled corticosteroid potent P-gp inducers especially

  14. Preparation of polymeric nanoparticles containing corticosteroid by a novel aerosol flow reactor method. (United States)

    Eerikäinen, Hannele; Kauppinen, Esko I


    Polymeric drug-containing nanoparticles were prepared using a novel aerosol flow reactor method. The polymeric drug-containing nanoparticles prepared consist of a poorly water soluble corticosteroid, beclomethasone dipropionate, and polymeric materials Eudragit E 100 or Eudragit L 100. The novel method used in this study allows synthesis of nanoparticles directly as dry powders. The nanoparticles can contain various ratios of drug and polymer, and the use of any additional stabilisation materials is avoided. In this study, nanoparticles with different drug-to-polymer ratios were prepared. Particle size and morphology, crystallinity, and thermal behaviour were determined as a function of particle composition. It was found that all the nanoparticles produced, regardless of particle composition, had geometric number mean diameters of approximately 90 nm, and were spherical showing smooth surfaces. The drug was molecularly dispersed in the amorphous polymeric matrix of the nanoparticles, and drug crystallisation was not observed when the ambient temperature was below the glass transition temperature of the polymer.

  15. Aerosol flow reactor method for synthesis of drug nanoparticles. (United States)

    Eerikäinen, Hannele; Watanabe, Wiwik; Kauppinen, Esko I; Ahonen, P Petri


    An aerosol flow reactor method, a one-step continuous process to produce nanometer-sized drug particles with unimodal size distribution, was developed. This method involves first dissolving the drug material in question into a suitable solvent, which is then followed by atomising the solution as fine droplets into carrier gas. A heated laminar flow reactor tube is used to evaporate the solvent, and solid drug nanoparticles are formed. In this study, the effect of drying temperature on the particle size and morphology was examined. A glucocorticosteroid used for asthma therapy, beclomethasone dipropionate, was selected as an experimental model drug. The geometric number mean particle diameter increases significantly with increasing reactor temperatures due to formation of hollow nanoparticles. Above 160 degrees C, however, further increase in temperature results in decreasing particle size. The produced nanoparticles are spherical and show smooth surfaces at all studied experimental conditions.

  16. Knemometry, urine cortisol excretion, and measures of the insulin-like growth factor axis and collagen turnover in children treated with inhaled glucocorticosteroids

    DEFF Research Database (Denmark)

    Wolthers, O D; Hansen, M; Juul, A


    . The study was a double blind, crossover trial with three active treatment periods and two wash-out periods. All periods were 15 d long. Overnight urine free cortisol/ creatinine x 10(6) did not correlate with knemometric growth rates or any of the serum markers. Significant correlations (Pearson......Correlations between knemometric (lower leg length) growth rates and urine free cortisol excretion, respectively, and serum concentrations of IGF-I, IGF binding protein-3, osteocalcin, carboxy terminal propeptide of type I collagen (PICP), carboxy terminal pryridinoline cross-linked telopeptide......'s correlation coefficient, P) between knemometric growth rates and IGF-I (0.41; 0.006), IGFBP-3 (0.35; 0.02), PICP (0.44; 0.003), ICTP (0.35; 0.001), and PIIINP (0.46; 0.002) were found. Compared with fluticasone propionate, 200 micrograms, beclomethasone dipropionate, 400 and 800 micrograms, caused significant...

  17. O impacto do tratamento fonoaudiológico no controle da asma e da rinite alérgica em crianças e adolescentes respiradores orais The impact of speech therapy on asthma and allergic rhinitis control in mouth breathing children and adolescents

    Directory of Open Access Journals (Sweden)

    Silvia M. A. Campanha


    quasi-experimental randomized study of 24 mouth breathing patients with asthma and allergic rhinitis, aged from 6 to 15 years. All patients were taking beclomethasone diproprionate through oral inhalation at the start of the study. At enrollment on the study, oral inhalation was substituted with exclusively nasal inhalation and 1 month later half of the patients began speech therapy. They attended 16 speech therapy sessions in 8 weeks and continued taking beclomethasone dipropionate through exclusively nasal inhalation (BDT group. The comparison group received only beclomethasone diproprionate through exclusively nasal inhalation (BDI group. Both groups were assessed five times. Clinical scores were calculated for allergic rhinitis and asthma, an adapted version of the Marchesan orofacial myofunctional assessment protocol was applied, and parents/guardians' observations were recorded, in addition to spirometry measurements of peak inspiratory and peak expiratory flow. RESULTS: There were significant improvements in the BDT group: clinical asthma score at T5 (p = 0.046; peak inspiratory flow at T4 (p = 0.030; peak expiratory flow at T3 (p = 0.008; breathing mode and lip position (p = 0.000 from T3 onwards; and parents/guardians' observations at T2, T4, and T5 (p = 0.010; p = 0.027; p = 0.030. CONCLUSIONS: Speech therapy in combination with beclomethasone diproprionate through exclusively nasal inhalation resulted in earlier and longer-lasting clinical and functional control of asthma, allergic rhinitis, and mouth breathing than was achieved in the group that only took beclomethasone diproprionate.

  18. Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Scichilone N


    Full Text Available Nicola Scichilone,1 Alida Benfante,1 Luca Morandi,2 Federico Bellini,2 Alberto Papi21Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Respiratory Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, ItalyAbstract: Asthma and chronic obstructive pulmonary disease (COPD are among the most common chronic diseases worldwide, characterized by a condition of variable degree of airway obstruction and chronic airway inflammation. A large body of evidence has demonstrated the importance of small airways as a pharmacological target in these clinical conditions. Despite a deeper understanding of the pathophysiological mechanisms, the epidemiological observations show that a significant proportion of asthmatic and COPD patients have a suboptimal (or lack of control of their diseases. Different factors could influence the effectiveness of inhaled treatment in chronic respiratory diseases: patient-related (eg, aging; disease-related (eg, comorbid conditions; and drug-related/formulation-related factors. The presence of multiple illnesses is common in the elderly patient as a result of two processes: the association between age and incidence of degenerative diseases; and the development over time of complications of the existing diseases. In addition, specific comorbidities may contribute to impair the ability to use inhalers, such as devices for efficient drug delivery in the respiratory system. The inability to reach and treat the peripheral airways may contribute to the lack of efficacy of inhaled treatments. The recent development of inhaled extrafine formulations allows a more uniform distribution of the inhaled treatment throughout the respiratory tree to include the peripheral airways. The beclomethasone/formoterol extrafine formulation is available for the treatment of asthma and COPD. Different biomarkers of peripheral airways are improved by beclomethasone

  19. LC-MS method for the simultaneous determination of six glucocorticoids in pharmaceutical formulations and counterfeit cosmetic products. (United States)

    Fiori, Jessica; Andrisano, Vincenza


    A screening method based on liquid chromatography-electrospray mass spectrometry for the simultaneous determination of six corticosteroids (betamethasone 17-valerate BM 17-V, beclomethasone BC, beclomethasone dipropionate BCDP, methylprednisolone MP, budesonide BD, flunisolide FN) was developed in order to control their illegal use in cosmetic and natural products. Indeed, despite corticosteroids are banned in cosmetics, counterfeit products might be present on the market, representing a health hazard. Therefore, effective analytical methods are required to rapidly screen over the counter products in health care shops for counterfeit corticosteroids. The analytical method involves the employment of a Waters Synergy C18 column (150mm×2.0mm I.D.) by using the following mobile phase: A (0.1% formic acid in acetonitrile), B (0.1% formic acid in water) in a linear gradient (from A-B 25:75, v/v to A-B 95:5, v/v in 30min) at the flow rate of 0.3mL/min. The detection was performed with an ion trap (IT) mass spectrometer in positive polarity, total ion current (TIC) and tandem mass modalities for qualitative purpose; single ion monitoring (SIM) mode was used for quantitative analysis on the ESI generated most abundant ion for each steroid. The method was fully validated in terms of precision, detection and quantification limits, linearity, recovery, and it was applied to the identification and quantification of corticosteroids in pharmaceutical formulations and cosmetic products. The mean recovery of BM 17-V, BC, BCDP, MP, BD and FN were found to be 101.3, 101.5, 98.8, 98.9, 98.1, 99.0%, respectively. Limits of quantitation (LOQ) were comprised in the range 29-95ng/mL. To the best of our knowledge, for the first time this mix of glucocorticoids were simultaneously determined in cosmetic products by using a fully validated method. BMV, in its two isomeric forms BM 17-V and BM 21-V, was found to be illegally present in one cream sample (A) with the total concentration level

  20. A comparison of techniques to assess skin blanching following the topical application of glucocorticoids. (United States)

    Noon, J P; Evans, C E; Haynes, W G; Webb, D J; Walker, B R


    Glucocorticoid-induced dermal blanching provides a useful research tool to study steroid potency and sensitivity. Conventional measurement of the intensity of blanching relies on subjective assessment by a trained observer using a visual score. Several objective techniques have recently been reported to detect skin blanching, but their sensitivity has not been compared previously with subjective visual recordings. In this report we aimed to establish whether objective methods offer sufficient sensitivity to be employed in epidemiological studies of glucocorticoid responsiveness. In healthy subjects we applied beclomethasone dipropionate at three concentrations (1, 10 and 100 micrograms/ml) under an occluded dressing overnight. The following morning we measured blanching using a visual score, laser Doppler velocimetry with the MBF 3D monitor (Moor Instruments Ltd, U.K.) and a perfusion imager (Lisca, Sweden), and reflectance spectrophotometry with the Dia-Stron 'erythemameter'. Using the visual score, blanching was detected at all concentrations of steroid. Neither laser Doppler instrument detected vasoconstriction at any concentration. By contrast, the reflectance spectrophotometer successfully recorded blanching at 10 and 100 micrograms/ml, but not at 1 microgram/ml. We conclude that laser Doppler instruments, including the novel scanning perfusion imager, do not detect glucocorticoid-induced skin blanching, perhaps because it reflects venular rather than arteriolar vasoconstriction. By contrast, the Dia-Stron reflectance spectrophotometer has sufficient sensitivity to be used as an alternative to visual assessment in epidemiological studies of human glucocorticoid-induced dermal blanching.

  1. A new method for liposome preparation using a membrane contactor. (United States)

    Jaafar-Maalej, Chiraz; Charcosset, Catherine; Fessi, Hatem


    In this article, we present a novel, scalable liposomal preparation technique suitable for the entrapment of pharmaceutical agents into liposomes. This new method is based on the ethanol-injection technique and uses a membrane contactor module, specifically designed for colloidal system preparation. In order to investigate the process, the influence of key parameters on liposome characteristics was studied. It has been established that vesicle-size distribution decreased with a decrease of the organic-phase pressure, an increase of the aqueous-phase flow rate, and a decrease of the phospholipid concentration. Additionally, special attention was paid on reproducibility and long-term stability of lipid vesicles, confirming the robustness of the membrane contactor-based technique. On the other hand, drug-loaded liposomes were prepared and filled with two hydrophobic drug models. High entrapment-efficiency values were successfully achieved for indomethacin (63%) and beclomethasone dipropionate (98%). Transmission electron microscopy images revealed nanometric quasispherical-shaped multilamellar vesicles (size ranging from 50 to 160 nm).

  2. Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers. (United States)

    Buttini, Francesca; Miozzi, Michele; Balducci, Anna Giulia; Royall, Paul G; Brambilla, Gaetano; Colombo, Paolo; Bettini, Ruggero; Forbes, Ben


    Solution composition alters the dynamics of beclomethasone diproprionate (BDP) particle formation from droplets emitted by pressurised metered dose inhalers (pMDIs). The hypothesis that differences in inhaler solutions result in different solid particle physical chemistry was tested using a suite of complementary calorimetric techniques. The atomisation of BDP-ethanol solutions from commercial HFA-pMDI produced aerodynamically-equivalent solid particle aerosols. However, differences in particle physico-chemistry (morphology and solvate/clathrate formation) were detected by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and supported by hot stage microscopy (HSM). Increasing the ethanol content of the formulation from 8 to 12% (w/w), which retards the evaporation of propellant and slows the increase in droplet surface viscosity, enhanced the likelihood of particles drying with a smooth surface. The dissolution rate of BDP from the 12% (w/w) ethanol formulation-derived particles (63% dissolved over 120 min) was reduced compared to the 8% (w/w) ethanol formulation-derived particles (86% dissolved over 120 min). The addition of 0.01% (w/w) formoterol fumarate or 1.3% (w/w) glycerol to the inhaler solution modified the particles and reduced the BDP dissolution rate further to 34% and 16% dissolved in 120 min, respectively. These data provide evidence that therapeutic aerosols from apparently similar inhaler products, including those with similar aerodynamic performance, may behave non-equivalently after deposition in the lungs.

  3. [Effect of basic therapy on clinical symptoms, quality of life and systemic inflammation in patients with chronic obstructive pulmonary disease]. (United States)

    Baranova, I I; Leshchenko, I V


    The study included 38 men with moderately severe chronic obstructive pulmonary disease (COPD) (mean age 60.6 ± 10.2 yr) and 42 ones with severe COPD (mean age 61.2 ± 7.2 yr). They were treated with tiotropium bromide, formoterol and beclomethasone dipropionate for 24 weeks (stage 1), TB alone for 12 weeks (stage 2) and TB+formoterol (long-acting bronchodilators, LABD) for another 12 weeks. Each stage was followed by evaluation of COPD symptoms using the St-George's Hospital questionnaire, daily requirements for short-acting beta-2 agonists (SABA), heart rate (HR), forced expiratory volume in the 1st second (FEV-1) before and after SABA test, hemoglobin saturation with oxygen in arterial blood during pulse oxymetry before and after 6 min walking test, blood surfactant protein D level (SP-D). The control group was comprised of 34 healthy men (mean age 62.3 ± 5.8 yr). Patients with moderately severe COPD experienced worsening of clinical symptoms (p COPD symptoms and HR was observed at stage 3. Alteration in the extent of basal therapy in patients with stage III COPD did not result in dynamics of clinical and laboratory characteristics. The data obtained suggest the necessity of combined therapy with LABD or triple basal therapy of moderately severe COPD and the possibility of therapy with one or two LABD having different sites of action in the patients with clinically stable stage II COPD.

  4. Effects of Steroids and Curcumin on Prevention of Laryngeal Stenosis Secondary to Trauma

    Directory of Open Access Journals (Sweden)

    Kamyar Iravani


    Full Text Available Introduction:  The aim of this study was to compare the preventive effects of corticosteroids and curcumin on subglottic stenosis in an animal model.  Materials and Methods: Twenty-one male German Shepherd dogs were used for this study. After standardized trauma to the subglottic area, the dogs were divided into three groups. Group A received curcumin (450 mg/ day for 15 days; Group B received beclomethasone (2 puffs/day, 50 µg/dose for 15 days; Group C received saline spray only. At 6 weeks after the injury, the larynx specimens were examined histopathologically to assess epithelialization, inflammation, and fibrosis.  Results: Complete epithelial covering of the steroid-treated group was significantly less than that of the control group. Despite inflammation and fibrosis, there was no significant difference between the steroid and control groups. In the curcumin-treated group, there was no significant difference between the groups.  Conclusion: Topically applied steroid decreases epithelialization after induced subglottic injury. It is recommended that further studies be conducted in order to investigate the effects of the two drugs on airway stenosis prevention.

  5. Effects of Steroids and Curcumin on Prevention of Laryngeal Stenosis Secondary to Trauma (United States)

    Iravani, Kamyar; Babaie, Zahra; Ashraf, Mohammad-Javad; Tanideh, Nader


    Introduction: The aim of this study was to compare the preventive effects of corticosteroids and curcumin on subglottic stenosis in an animal model. Materials and Methods: Twenty-one male German Shepherd dogs were used for this study. After standardized trauma to the subglottic area, the dogs were divided into three groups. Group A received curcumin (450 mg/ day) for 15 days; Group B received beclomethasone (2 puffs/day, 50 µg/dose) for 15 days; Group C received saline spray only. At 6 weeks after the injury, the larynx specimens were examined histopathologically to assess epithelialization, inflammation, and fibrosis. Results: Complete epithelial covering of the steroid-treated group was significantly less than that of the control group. Despite inflammation and fibrosis, there was no significant difference between the steroid and control groups. In the curcumin-treated group, there was no significant difference between the groups. Conclusion: Topically applied steroid decreases epithelialization after induced subglottic injury. It is recommended that further studies be conducted in order to investigate the effects of the two drugs on airway stenosis prevention. PMID:27602335

  6. Symptoms, but Not a Biomarker Response to Inhaled Corticosteroids, Predict Asthma in Preschool Children with Recurrent Wheeze

    Directory of Open Access Journals (Sweden)

    E. M. M. Klaassen


    Full Text Available Background. A reliable asthma diagnosis is challenging in preschool wheezing children. As inhaled corticosteroids (ICS are more effective in asthmatics than in children with transient wheeze, an ICS response might be helpful in early asthma diagnosis. Methods. 175 children (aged two–four years with recurrent wheeze received 200 μg Beclomethasone extra-fine daily for eight weeks. Changes in Exhaled Breath Condensate (EBC biomarkers (pH, interleukin (IL-1α, IL-2, IL-4, IL-5, IL-10, IFN-γ, sICAM, and CCL-11, Fractional exhaled Nitric Oxide (FeNO, airway resistance, and symptoms were assessed. At six years of age a child was diagnosed as transient wheezer or asthmatic. Adjusted logistic regression analysis was performed with multiple testing correction. Results. 106 transient wheezers and 64 asthmatics were analysed at six years of age. Neither changes in EBC biomarkers, nor FeNO, airway resistance, or symptoms during ICS trial at preschool age were related to asthma diagnosis at six years of age. However, asthmatics had more airway symptoms before the start of the ICS trial than transient wheezers (P<0.01. Discussion. Although symptom score in preschool wheezing children at baseline was associated with asthma at six years of age, EBC biomarkers, airway resistance, or symptom response to ICS at preschool age could not predict asthma diagnosis at six years of age.

  7. Engineering of drug nanoparticles by HGCP for pharmaceutical applications

    Institute of Scientific and Technical Information of China (English)

    TingTing Hu; JieXin Wang; ZhiGang Shen; JianFeng Chen


    This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nenoparticles, which was carded out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxirne Axetil (CFA) particles, 200-400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), end 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation end drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing end the ease of scaling-up.

  8. Steroid-decorated antibiotic microparticles for inhaled anti-infective therapy. (United States)

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Zhao, Yanli; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B H


    Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention. Unfortunately, no combined steroid-antibiotic dry powder formulation is available commercially or has been reported in the academic literature. The aim of this work was hence to develop a novel steroid-antibiotic dry powder inhaler formulation [ciprofloxacin hydrochloride (CIP) and beclomethasone dipropionate (BP)] for inhaled anti-infective therapy. The spray-dried powder was of respirable size (d50 of ∼2.3 μm), partially crystalline and had BP preferentially deposited on the particle surface. Favorably, when formulated as a binary mix, both CIP and BP showed much higher drug release and fine particle fractions (of the loaded dose) over their singly delivered counterparts, and had robust activity against the respiratory tract infection-causing bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

  9. Dispersibility of lactose fines as compared to API in dry powders for inhalation. (United States)

    Thalberg, Kyrre; Åslund, Simon; Skogevall, Marcus; Andersson, Patrik


    This work investigates the dispersion performance of fine lactose particles as function of processing time, and compares it to the API, using Beclomethasone Dipropionate (BDP) as model API. The total load of fine particles is kept constant in the formulations while the proportions of API and lactose fines are varied. Fine particle assessment demonstrates that the lactose fines have higher dispersibility than the API. For standard formulations, processing time has a limited effect on the Fine Particle Fraction (FPF). For formulations containing magnesium stearate (MgSt), FPF of BDP is heavily influenced by processing time, with an initial increase, followed by a decrease at longer mixing times. An equation modeling the observed behavior is presented. Surprisingly, the dispersibility of the lactose fines present in the same formulation remains unaffected by mixing time. Magnesium analysis demonstrates that MgSt is transferred to the fine particles during the mixing process, thus lubrication both BDP and lactose fines, which leads to an increased FPF. Dry particle sizing of the formulations reveals a loss of fine particles at longer mixing times. Incorporation of fine particles into the carrier surfaces is believed to be behind this, and is hence a mechanism of importance as regards the dispersion performance of dry powders for inhalation.

  10. Expired nitric oxide levels in adult asthmatics

    Directory of Open Access Journals (Sweden)

    Chiharu Okada


    Full Text Available The expired nitric oxide (NO concentration is known to be higher in asthmatic subjects than in normal subjects. To elucidate the role of NO in asthma, we examined the expired NO concentrations in relation to the type (atopic, mixed, non- atopic, and severity (mild, moderate, severe of asthmatics, as well as the influence of steroid treatment. Twenty-seven normal subjects, 48 asthmatics, 8 subjects with allergic rhinitis, and 13 subjects with pulmonary emphysema participated in the study. The expired NO concentration was significantly higher in asthmatics and patients with allergic rhinitis than in normal subjects (P<0.01. No significant difference was observed between the expired NO concentration in patients with pulmonary emphysema and that of normal subjects. The expired NO concentrations were significantly lower in non- atopic asthma than in atopic asthma. Nitric oxide levels were significantly lower in severe asthma than in mild asthma. High doses of steroid treatment are often used in severe asthma. The dose of inhaled beclomethasone and expired NO concentrations showed a negative correlation (r= −0.51587, P<0.004. Drip infusion of hydrocortisone tended to increase the exhaled NO concentration just after drip infusion, however, it decreased after 24 h. These results suggest that steroid treatment decreases the expired NO concentrations in asthmatics, although it cannot be concluded that NO increases the severity of asthma. The measurement of expired NO concentrations is an easy, non-invasive test, which may be a useful tool for monitoring the condition of asthmatics.

  11. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

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    Mazzarino, Monica [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Rossi, Francesca [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Giacomelli, Laura [Dipartimento di Scienze Chirurgiche, Universita La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Botre, Francesco [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy) and Dipartimento CGMIA, Universita La Sapienza, Via del Castro Laurenziano 9, 00161 Rome (Italy)]. E-mail:


    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation.

  12. Treatment of allergic rhinitis during pregnancy. (United States)

    Demoly, Pascal; Piette, Vincent; Daures, Jean-Pierre


    Allergic rhinitis is a frequent problem during pregnancy. In addition, physiological changes associated with pregnancy can affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have recently been published, the most recent being the Allergic Rhinitis and its Impact on Asthma (ARIA)--World Health Organization consensus. Many pregnant women experience allergic rhinitis and particular attention is required when prescribing drugs to these patients. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one drug from each major class that can be safely utilised to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (e.g. beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few histamine H(1)-receptor antagonists (H(1)-antihistamines) can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intra-nasal decongestants. Finally, pregnancy is not considered as a contraindication for the continuation of allergen specific immunotherapy.

  13. Treating allergic rhinitis in pregnancy. (United States)

    Piette, Vincent; Daures, Jean-Pierre; Demoly, Pascal


    Numerous pregnant women suffer from allergic rhinitis, and particular attention is required when prescribing drugs to these patients. In addition, physiologic changes associated with pregnancy could affect the upper airways. Evidence-based guidelines on the management of allergic rhinitis have been published. Medication can be prescribed during pregnancy when the apparent benefit of the drug is greater than the apparent risk. Usually, there is at least one "safe" drug from each major class used to control symptoms. All glucocorticosteroids are teratogenic in animals but, when the indication is clear (for diseases possibly associated, such as severe asthma exacerbation), the benefit of the drug is far greater than the risk. Inhaled glucocorticosteroids (eg, beclomethasone or budesonide) have not been incriminated as teratogens in humans and are used by pregnant women who have asthma. A few H1-antihistamines can safely be used as well. Most oral decongestants (except pseudoephedrine) are teratogenic in animals. There are no such data available for intranasal decongestants. Finally, pregnancy is not considered to be a contraindication for the continuation of immunotherapy.

  14. Evaluation of factors that allow the clinician to taper inhaled corticosteroids in childhood asthma

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    Kentaro Matsuda


    Full Text Available Inhaled corticosteroids are potent and effective treatment agents for controlling symptoms of childhood asthma. However, there are no predictive factors that help to determine which patients with asthma are likely to be tapered off inhaled corticosteroids successfully. We examined whether any factor or combination of factors could help the clinician safely discontinue inhaled steroid therapy. Thirty-six asthmatic children whose symptoms were stable on low-dose beclomethasone dipropionate (BDP were divided by parental choice into two groups: maintenance BDP (n = 11 and no BDP (n = 25. Methacholine inhalation tests were performed at the beginning of the study and after 1 month. Twelve children (48% who had BDP discontinued developed exacerbations after 2–3 months, whereas there were no problems in the maintenance group. The no BDP group was retrospectively divided into two subgroups: exacerbation (+ and (−. The threshold to methacholine in the exacerbation (+ subgroup decreased significantly in advance of clinical symptoms. The two subgroups were analyzed statistically by two-group discriminant function analysis. The change in threshold to methacholine, the dose and potency of drugs, duration of asthma and gender (female correlated with exacerbation. These results suggest that discontinuation of inhaled steroids should be done carefully, even in stable asthmatic children. The methacholine inhalation test, gender, drugs and history may be used as references for discontinuing inhaled steroids.

  15. The progress of inhaled corticosteroid/long-actingβ2-agonist combinations in the treatment of asthma%吸入糖皮质激素和长效β2-受体激动剂复方制剂治疗哮喘的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙伟; 揭志军


    联合使用吸入糖皮质激素和长效β2-受体激动剂对控制哮喘的气道炎症和改善气道平滑肌功能具有协同和互补作用。吸入糖皮质激素和长效β2-受体激动剂复方制剂是目前哮喘维持治疗的重要药物,主要包括丙酸氟替卡松/沙美特罗、布地奈德/福莫特罗、二丙酸倍氯松/福莫特罗和糠酸莫米松/福莫特罗等。本文就此类复方制剂在哮喘治疗中的临床地位和研究进展作一概述。%Inhaled corticosteroid/long-actingβ2-agonist (ICS/LABA) combinations play synergic and complementary roles in controlling airway inlfammation and improving the function of airway smooth muscle. They are very important drugs for asthma maintenance. The different combinations of ICS/LABA, such as lfuticasone propionate/salmeterol, budesonide/formoterol, beclomethasones dipropionate/formoterol, mometasone furoate/formoterol, have different pharmacological features. This review summarizes the features and progress of these ICS/LABA in the treatment of asthma.

  16. Internal exposure dynamics drive the Adverse Outcome Pathways of synthetic glucocorticoids in fish (United States)

    Margiotta-Casaluci, Luigi; Owen, Stewart F.; Huerta, Belinda; Rodríguez-Mozaz, Sara; Kugathas, Subramanian; Barceló, Damià; Rand-Weaver, Mariann; Sumpter, John P.


    The Adverse Outcome Pathway (AOP) framework represents a valuable conceptual tool to systematically integrate existing toxicological knowledge from a mechanistic perspective to facilitate predictions of chemical-induced effects across species. However, its application for decision-making requires the transition from qualitative to quantitative AOP (qAOP). Here we used a fish model and the synthetic glucocorticoid beclomethasone dipropionate (BDP) to investigate the role of chemical-specific properties, pharmacokinetics, and internal exposure dynamics in the development of qAOPs. We generated a qAOP network based on drug plasma concentrations and focused on immunodepression, skin androgenisation, disruption of gluconeogenesis and reproductive performance. We showed that internal exposure dynamics and chemical-specific properties influence the development of qAOPs and their predictive power. Comparing the effects of two different glucocorticoids, we highlight how relatively similar in vitro hazard-based indicators can lead to different in vivo risk. This discrepancy can be predicted by their different uptake potential, pharmacokinetic (PK) and pharmacodynamic (PD) profiles. We recommend that the development phase of qAOPs should include the application of species-species uptake and physiologically-based PK/PD models. This integration will significantly enhance the predictive power, enabling a more accurate assessment of the risk and the reliable transferability of qAOPs across chemicals.

  17. Patient perspectives in the management of asthma: improving patient outcomes through critical selection of treatment options

    Directory of Open Access Journals (Sweden)

    Nicola Scichilone


    Full Text Available Nicola Scichilone, Adele Contino, Giovanni Battista Figlioli, Giuseppe Paglino, Vincenzo BelliaDipartimento di Medicina, Pneumologia, Fisiologia e Nutrizione Umana (DIMPEFINU, University of Palermo, Palermo, ItalyAbstract: Asthma is a chronic inflammatory disorder of the airways that requires long-term treatment, the goal of which is to control clinical symptoms for extended periods with the least possible amount of drugs. International guidelines recommend the addition of an inhaled long-acting beta2-agonist (LABA to a low- to medium-dose inhaled corticosteroid (ICS when low doses of ICS fail to control asthma symptoms. The fixed combined administration of ICS/LABA improves patient compliance, reducing the risk of therapy discontinuation. The relative deposition pattern of the inhaled drug to the target site is the result of a complex interaction between the device used, the aerosol formulation and the patient’s adherence to therapy. Different inhalation devices have been introduced in clinical practice over time. The new hydrofluoroalkane (HFA solution aerosols allow for the particle size to be modified, thus leading to deeper penetration of the medication into the lung. The Modulite® technology allows for the manipulation of inhaled HFA-based solution formulations, such as the fixed beclomethasone/formoterol combination, resulting in a uniform treatment of inflammation and bronchoconstriction. The success of any anti-asthmatic treatment depends on the choice of the correct device and the adherence to therapy.Keywords: asthma, therapy, inhalers, compliance

  18. Separation and pre-concentration of glucocorticoids in water samples by ionic liquid supported vortex-assisted synergic microextraction and HPLC determination. (United States)

    Qin, Hui; Li, Bi; Liu, Mou Sheng; Yang, Ya Ling


    We have developed a synergic microextraction procedure based on ionic liquid for the pre-concentration and determination of glucocorticoids in water samples. Using nonionic surfactant Triton X-100 (TX-100) as synergic reagent, 1-butyl-3-methylimidazolium hexa-fluorophosphate accomplished extraction rapidly without heating in water bath. One key property of ionic liquids that highlights their potential is their wide liquid temperature range. The improved extraction was named as ionic liquid supported vortex-assisted synergic microextraction. Compared with the traditional liquid-liquid extraction and cloud point extraction, ionic liquid supported vortex-assisted synergic microextraction was accomplished in 8 min with considerably high recovery. The proposed method greatly improved the sensitivity of HPLC for the determination of glucocorticoids. The results obtained indicated a good linearity with the correlation coefficient of 0.997 over the range of 0.6-300 ng/mL and high sensitivity with LODs of 4.11, 9.19, and 7.50 ng/mL for hydrocortisone butyrate, beclomethasone dipropionate, and nandrolone phenylpropionate, respectively. The RSD of the method was 1.57-1.81% (n = 6) with enrichment factor of 99.85, and good recovery (≥97.24%). The method was successfully applied to the determination of glucocorticoids in mineral water, water of Dianchi lake, and tap water samples.

  19. A rapid and sensitive HPLC-APCI-MS/MS method determination of fluticasone in human plasma: application for a bioequivalency study in nasal spray formulations. (United States)

    Byrro, Ricardo Martins Duarte; César, Isabela Costa; de Santana e Silva Cardoso, Fabiana Fernandes; Mundim, Iram Moreira; Teixeira, Leonardo de Souza; Bonfim, Ricardo Rodrigues; Gomes, Sandro Antônio; Pianetti, Gerson Antônio


    A sensitive method for the determination of fluticasone in plasma was developed using high performance liquid chromatography with tandem mass spectrometric detection, whereas beclomethasone was used as internal standard. The analytes were extracted with a simple liquid-liquid extraction from the plasma samples and separated on an ACE C(18) 50 × 4.6 mm i.d.; 5 μm particle size column with a mobile phase consisting of acetonitrile - 0.01% formic acid (48:52, v/v) at a flow rate of 1 ml/min. Detection was achieved by an Applied Biosystems API 5000 mass spectrometer (LC-MS/MS) set at unit resolution in the multiple reaction monitoring mode. Atmospheric pressure chemical ionization (APCI) was used for ion production. The mean recovery for fluticasone propionate was 85%, with a lower limit of quantification set at 2 pg/mL. The validated analytical method was applied to a bioequivalence study of fluticasone propionate administered by nasal spray formulations in human volunteers.

  20. Isothermal calorimetry: a predictive tool to model drug-propellant interactions in pressurized metered dose systems. (United States)

    Ooi, Jesslynn; Gaisford, Simon; Boyd, Ben J; Young, Paul M; Traini, Daniela


    The purpose of this work was to evaluate gas perfusion isothermal calorimetry (ITC) as a method to characterize the physicochemical changes of active pharmaceutical ingredients (APIs) intended to be formulated in pressurized metered dose inhalers (pMDIs) after exposure to a model propellant. Spray dried samples of beclomethasone dipropionate (BDP) and salbutamol sulphate (SS) were exposed to controlled quantities of 2H,3H-decafluoropentane (HPFP) to determine whether ITC could be used as a suitable analytical method for gathering data on the behavioural properties of the powders in real time. The crystallization kinetics of BDP and the physiochemical properties of SS were successfully characterized using ITC and supported by a variety of other analytical techniques. Correlations between real and model propellant systems were also established using hydrofluoroalkane (HFA-227) propellant. In summary, ITC was found to be suitable for gathering data on the crystallization kinetics of BDP and SS. In a wider context, this work will have implications on the use of ITC for stability testing of APIs in HFA-based pMDIs.

  1. Switching patients from other inhaled corticosteroid devices to the Easyhaler®: historical, matched-cohort study of real-life asthma patients

    Directory of Open Access Journals (Sweden)

    Price D


    Full Text Available David Price,1,2 Vicky Thomas,2 Julie von Ziegenweidt,2 Shuna Gould,2 Catherine Hutton,2 Christine King2 1Academic Centre of Primary Care, University of Aberdeen, Aberdeen, UK; 2Research in Real Life, Oakington, Cambridge, UK Purpose: To investigate the clinical and cost effectiveness of switching real-life asthma patients from other types of inhalers to the Easyhaler® (EH for the administration of inhaled corticosteroids (ICS. Patients and methods: Historical, matched-cohort study of 1,958 asthma patients (children and adults treated in UK primary-care practices, using data obtained from the Optimum Patient Care Research Database and Clinical Practice Research Datalink. Other inhalers (OH included pressurized metered-dose inhalers, breath-actuated inhalers, and dry-powder inhalers, delivering beclomethasone, budesonide, fluticasone, or ciclesonide. Patients remaining on OH unchanged (same drug, dosage, and device; n=979 were matched 1:1 with those switched to the EH (beclomethasone or budesonide at the same or lower ICS dosage (n=979, based on age, sex, year of index patient review/switch, most recent ICS drug, dosage, and device, and the number of severe exacerbations and average daily short-acting β2 agonist (SABA dosage in the preceding year. Clinical outcomes and health care costs were compared between groups for 12 months before and after the switch. Co-primary clinical outcomes were: 1 risk domain asthma control (RDAC – no asthma-related hospitalization, acute oral steroid use, or lower respiratory tract infection (LRTI; 2 exacerbation rate (American Thoracic Society [ATS] definition – where exacerbation is asthma-related hospitalization or acute oral steroid use; 3 exacerbation rate (clinical definition – where exacerbation is ATS exacerbation or LRTI; and 4 overall asthma control (OAC – RDAC plus average salbutamol-equivalent SABA dosage ≤200 μg/day. Non-inferiority (at least equivalence of EH was tested against OH for the

  2. Diagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines. (United States)

    Kankaanranta, Hannu; Harju, Terttu; Kilpeläinen, Maritta; Mazur, Witold; Lehto, Juho T; Katajisto, Milla; Peisa, Timo; Meinander, Tuula; Lehtimäki, Lauri


    of an inhaled glucocorticoid and a long-acting β2 -agonist (budesonide-formoterol, beclomethasone dipropionate-formoterol, fluticasone propionate-salmeterol or fluticasone furoate-vilanterol) is recommended as a first choice. Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium-indacaterol or umeclidinium-vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2 -agonist and a long-acting anticholinergic. If the patient has severe-to-very severe COPD (FEV1  COPD in which there are features that comply with both asthma and COPD. Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD. Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2 -agonist or anticholinergic or both).

  3. Zebrafish Expression Ontology of Gene Sets (ZEOGS): a tool to analyze enrichment of zebrafish anatomical terms in large gene sets. (United States)

    Prykhozhij, Sergey V; Marsico, Annalisa; Meijsing, Sebastiaan H


    The zebrafish (Danio rerio) is an established model organism for developmental and biomedical research. It is frequently used for high-throughput functional genomics experiments, such as genome-wide gene expression measurements, to systematically analyze molecular mechanisms. However, the use of whole embryos or larvae in such experiments leads to a loss of the spatial information. To address this problem, we have developed a tool called Zebrafish Expression Ontology of Gene Sets (ZEOGS) to assess the enrichment of anatomical terms in large gene sets. ZEOGS uses gene expression pattern data from several sources: first, in situ hybridization experiments from the Zebrafish Model Organism Database (ZFIN); second, it uses the Zebrafish Anatomical Ontology, a controlled vocabulary that describes connected anatomical structures; and third, the available connections between expression patterns and anatomical terms contained in ZFIN. Upon input of a gene set, ZEOGS determines which anatomical structures are overrepresented in the input gene set. ZEOGS allows one for the first time to look at groups of genes and to describe them in terms of shared anatomical structures. To establish ZEOGS, we first tested it on random gene selections and on two public microarray datasets with known tissue-specific gene expression changes. These tests showed that ZEOGS could reliably identify the tissues affected, whereas only very few enriched terms to none were found in the random gene sets. Next we applied ZEOGS to microarray datasets of 24 and 72 h postfertilization zebrafish embryos treated with beclomethasone, a potent glucocorticoid. This analysis resulted in the identification of several anatomical terms related to glucocorticoid-responsive tissues, some of which were stage-specific. Our studies highlight the ability of ZEOGS to extract spatial information from datasets derived from whole embryos, indicating that ZEOGS could be a useful tool to automatically analyze gene expression

  4. Flow cytometric analysis of lymphocytes and lymphocyte subpopulations in induced sputum from patients with asthma

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    Yutaro Shiota


    Full Text Available Study objectives were to compare the numbers of lymphocytes and lymphocyte subpopulations in induced sputum from asthmatic patients and from healthy subjects, and to determine the effect of inhaled anti-asthmatic steroid therapy on these cell numbers. Hypertonic saline inhalation was used to non-invasively induce sputum samples in 34 patients with bronchial asthma and 21 healthy subjects. The sputum samples were reduced with dithioerythritol and absolute numbers of lymphocytes and lymphocyte subpopulations were assessed by direct immunofluorescence and flow cytometry. To assess the effect of beclomethasone dipropionate (BDP on induced sputum, numbers of lymphocytes and lymphocyte subpopulations in sputum also were evaluated after 4 weeks of BDP inhalation treatment in seven asthmatic patients. An adequate sample was obtained in 85.3% of patients with asthma and in 79.2% of the healthy subjects. Induced sputum from patients with asthma had increased numbers of lymphocytes (P = 0.009; CD4+ cells (P = 0.044; CD4+ cells-bearing interleukin-2 receptor (CD25; P = 0.016; and CD4+ cells bearing human histocompatibility leukocyte antigen (HLA-DR (P = 0.033. CD8+ cells were not increased in asthmatic patients. In patients treated with inhaled steroids, numbers of lymphocytes, CD4+ cells, CD25-bearing CD4+ cells and HLA-DR-bearing CD4+ cells in sputum decreased from pretreatment numbers (P = 0.016, 0.002, 0.003 and 0.002, respectively. Analysis of lymphocytes in induced sputum by flow cytometry is useful in assessing bronchial inflammation, and activated CD4+ lymphocytes may play a key role in the pathogenesis of airway inflammation in bronchial asthma.

  5. Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT(1) antagonist, pranlukast, in Japanese patients with moderate asthma. (United States)

    Asano, Koichiro; Shiomi, Tetsuya; Hasegawa, Naoki; Nakamura, Hidetoshi; Kudo, Hiroyasu; Matsuzaki, Tatsu; Hakuno, Haruhiko; Fukunaga, Kouichi; Suzuki, Yusuke; Kanazawa, Minoru; Yamaguchi, Kazuhiro


    CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.

  6. The developing Xenopus limb as a model for studies on the balance between inflammation and regeneration. (United States)

    King, Michael W; Neff, Anton W; Mescher, Anthony L


    The roles of inflammation and immune cell reactivity triggered by amputation have only recently begun to be addressed in investigations of epimorphic regeneration, although studies of tissue repair in mammals clearly show the importance of the immune system in determining the quality of the repair process. Here, we first review inflammation-related work in non-mammalian systems of epimorphic regeneration which suggests that regeneration of an amputated appendage requires continuous modulation of the local immune response, from the first hours after amputation through the period of blastema patterning. We then present data on the effects of anti-inflammatory and proinflammatory agents on regeneration of larval Xenopus hindlimbs. Treatment with the glucocorticoid beclomethasone immediately after amputation inhibits regeneration in regeneration-complete stage 53 limbs. Other anti-inflammatory agents, including the inhibitors of cyclooxygenase-2 (COX-2) activity celecoxib and diclofenac, applied similarly to larvae amputated at stage 55, when the capacity for limb regeneration is normally being lost, restore regenerative capacity. This suggests that although injury-related events sensitive to glucocorticoids are necessary for regeneration, resolution of the inflammatory response may also be required to allow the complete regenerative response and normal blastema patterning. Conversely, if resolution of inflammation is prevented by local treatment of amputated limbs with beryllium, a strong immunoadjuvant, regeneration is inhibited, and gene expression data suggest that this inhibition results from a failure of normal blastema patterning. Both positive and negative effects of immune- or inflammation-related activities occur during anuran limb regeneration and this underscores the importance of considering immune cells in studies of epimorphic regeneration.

  7. Long-term (5 year safety of bronchial thermoplasty: Asthma Intervention Research (AIR trial

    Directory of Open Access Journals (Sweden)

    Pavord Ian D


    Full Text Available Abstract Background Bronchial thermoplasty (BT is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure. Methods Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs and spirometry data were used to assess long-term safety out to 5 years post-BT. Results 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,. There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group. Conclusions The absence of clinical complications (based on AE reporting and the maintenance of stable lung function (no deterioration of FVC and FEV1 over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.

  8. Effects of nebulized sodium cromoglycate on adult patients with severe refractory asthma. (United States)

    Sano, Yasuyuki; Adachi, Mitsuru; Kiuchi, Takahiro; Miyamoto, Terumasa


    Many patients with severe refractory asthma, which is insufficiently controlled by additional high-dose of inhaled corticosteroids, require oral corticosteroids and/or immunosuppressant. Clinicians should seek for suitable medications, for its' chronic use may induce high risk of side effects. The purpose of this study was to evaluate the efficacy and safety of nebulized sodium cromoglycate (3-4 times/day) in adult severe asthmatic patients with poorly controlled asthmatic symptoms, despite treatments with high-dose inhaled corticosteroids. Adult patients with severe asthma (n=251) were enrolled in a randomized clinical trial at 30 medical centers in Japan. Isotonic saline was used as placebo. The study was conducted for 10 weeks; with initial 2 weeks of observation followed by 8 weeks of treatments. Efficacy was primarily evaluated based on improvements in morning peak expiratory flow after treatment. All patients who applied inhalation of nebulized sodium cromoglycate (SCG group) or saline (Controls) were treated with high-dose of inhaled corticosteroids (median of beclomethasone dipropionate equivalent dose: 1600 microg/days) and second-line control therapy including oral corticosteroids. There was no significant difference in morning peak expiratory flow between SCG group and controls. However, when patients were stratified into atopic and non-atopic groups, morning peak expiratory flow had significantly improved in the atopic SCG group compared to atopic Controls. Additional inhalation of nebulized sodium cromoglycate with inhaled corticosteroids is effective even in patients with severe atopic asthma. This finding shows that nebulized sodium cromoglycate is expected to be new second-line therapeutic option in severe asthma.

  9. 止喘汤减少糖皮质激素吸入量治疗支气管哮喘的临床研究%Zhichuan decoction with glucocorticoid in treatment of bronchial asthma

    Institute of Scientific and Technical Information of China (English)

    王庆; 李一; 霍博雅; 郭汉卿; 寇伟莉


    Three hundred and ninety five patients with bronchial asthma were randomly divided into 4 groups:patients in group A received inhaled beclomethasone dipropionate(BDP)100μg and Zhichuan decoction;patients in group B were given inhaled BDP 200μg;patients in group C took Zhichuan decoction only;patients in group D were given inhaled BDP 100 μg.Methacholine airway reactivity,pulmonary ventilation function,serum acidophilia cationic protein and symptom score were determined before and after treatment.All above indicators were significantly improved in groups A and B,which suggests that Zhichuan decoction could reduce hormone dosage in control of airway chronic inflammation,reduction of airway reactivity and improvement of pulmonary ventilation function of patients with bronchial asthma.%将395例哮喘患者随机分为4组,A组在吸入二丙酸倍氯米松100μg的同时服用止喘汤,B、C、D组分别单纯吸入二丙酸倍氯米松200μg、服用止喘汤、吸入二丙酸倍氯米松100μg.A、B组患者治疗前后乙酰甲胆碱气道反应性、肺通气功能、血清嗜酸性阳离子蛋白及症状积分均有明显改善.提示止喘汤在减少糖皮质激素吸入量的同时能控制气道慢性炎症、降低气道反应性、提高患者肺通气功能.

  10. Cluster Analysis and Clinical Asthma Phenotypes (United States)

    Shaw, Dominic E.; Berry, Michael A.; Thomas, Michael; Brightling, Christopher E.; Wardlaw, Andrew J.


    Rationale Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model. Objectives To explore the application of a multivariate mathematical technique, k-means cluster analysis, for identifying distinct phenotypic groups. Methods We performed k-means cluster analysis in three independent asthma populations. Clusters of a population managed in primary care (n = 184) with predominantly mild to moderate disease, were compared with a refractory asthma population managed in secondary care (n = 187). We then compared differences in asthma outcomes (exacerbation frequency and change in corticosteroid dose at 12 mo) between clusters in a third population of 68 subjects with predominantly refractory asthma, clustered at entry into a randomized trial comparing a strategy of minimizing eosinophilic inflammation (inflammation-guided strategy) with standard care. Measurements and Main Results Two clusters (early-onset atopic and obese, noneosinophilic) were common to both asthma populations. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation (early-onset symptom predominant and late-onset inflammation predominant) were specific to refractory asthma. Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster (3.53 [SD, 1.18] vs. 0.38 [SD, 0.13] exacerbation/patient/yr, P = 0.002) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster (mean difference, 1,829 μg beclomethasone equivalent/d [95% confidence interval, 307–3,349 μg]; P = 0.02). Conclusions Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms. PMID:18480428

  11. Supramolecular solvent-based vortex-mixed microextraction: determination of glucocorticoids in water samples. (United States)

    Qin, Hui; Qiu, Xiaoyan; Zhao, Jiao; Liu, Mousheng; Yang, Yaling


    Glucocorticoids contamination has become a big environmental issue in China and other developing countries, due to increasing needs in medical prescription and farming. However, no highly sensitive and precise methods have been reported to quantify glucocorticoids so far. In the past several years, supramolecular solvent-based vortex-mixed microextraction (SS-BVMME) has been shown to be effective. However, the mechanism of SS-BVMME is still unknown. In this report, a novel method has been proposed for rapid quantification of trace amount of glucocorticoids, beclomethasone dipropionate (BD), hydrocortisone butyrate (HB) and nandrolone phenylpropionate (NPP) in water samples from the Green Lake. This method is simple, safe and cost effective. It contains two steps: supramolecular solvent-based vortex-mixed microextraction (SS-BVMME) technique and high performance liquid chromatography (HPLC) analysis. First, ionic liquids 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) and n-butanol were mixed to form the supramolecular solvent. After mixing the supramolecular solvent with an aqueous sample to test, a homogenous mixture was formed immediately. BD, HB and NPP were then extracted based on their binding interactions, particularly hydrogen bond formed between their hydroxyl group and the supramolecular solvent. The overall process of sample preparation took only 20min and more than 5 samples could be simultaneously prepared. The minimum detectable concentrations of samples in this method were 0.09925, 0.5429 and 2.428ngmL(-1) for BD, HB and NPP, respectively. Product recoveries ranged from 88% to 103% with relative standard deviations from 0.6% to 4%. For the first time, we report that hydrogen bond plays a key role in SS-BVMME. We also improve the sensitivity significantly to quantify glucocorticoids, which may greatly benefit environmental safety management in China.

  12. Systematic reviews on efficacy and safety of beclomethosone nasal spray in the treatment of chronic adenoid hypertrophy in children%倍氯米松鼻喷剂治疗儿童腺样体肥大的系统评价

    Institute of Scientific and Technical Information of China (English)

    米姣平; 樊韵平; 王静清; 夏文彤


    Objective To systematically review the efficacy and safety of beclomethosone nasal spray in the treatment of chronic adenoid hypertrophy in children. Methods We computerized searches of the Cochrane Central Register of ControUed Trials (CENTRAL) (issue1,009), MEDLINE (1950 to August 2008) ,EMbase (1984 to August 2008), CNKI (1994 to September 2008), and VIP (1989 to August 2008), WANFANG DATA, Annual Review-s and Elsevier Science. Also the reference lists of all papers were identified for further trials. All searches were initially performed in May 2007 and updated in April 2009. Randomized controlled trials (RCT) and quasi-RCTs were identified and analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions. Results Three RCT were included. Meta-analysis was not performed due to heterogeneity and the data were summarized in a narrative formal The trials showed that higher doses of beclomethasone (336 μg/d, 400 μg/d) might improve the nasal obstruction symptoms and reduce adenoid size in children with adenoid hypertrophy. Conclusions Higher and subsequently half doses of beclomethasone (336 g/d, 400 g/d) can improve the nasal obstruction symptoms in children with adenoid hypertrophy. The improvement appears to be associated with a reduction of adenoid size. Beacuse of a lack of the RCT, further studies are required to support the use of beclomethasone as a first-line approach for these children.%目的 系统评价局部使用倍氯米松气雾剂对儿童腺样体肥大的有效性、安全性.方法 计算机检索临床随机对照试验资料库Cochrane图书馆、MEDLINE、EMbase、维普中文期刊数据库(VIP)、万方学位论文数据库、中国期刊全文数据库(CNKI)、中国医疗健康年库等,并辅以手工检索相关会议论文集、药厂资料及所有检索到的文献的参考文献.检索截至2009年1月.收集倍氯米松鼻喷雾剂对腺样体肥大治疗作用的随机对照试验(RCT)及半随机对照

  13. Quantitative determination of betamethasone sodium phosphate and betamethasone dipropionate in human plasma by UPLC-MS/MS and a bioequivalence study. (United States)

    Chen, Man-Yun; Tang, Yong-Jun; Wang, Yi-Cheng; Wang, Chong-Zhi; Yuan, Chun-Su; Chen, Yao; Tan, Zhi-Rong; Huang, Wei-Hua; Zhou, Hong-Hao


    The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and chronic diseases such as asthma, rheumatoid arthritis and systemic lupus erythematosus. It will be useful and beneficial to validate sensitive method for the determination of BSP, BDP and their metabolites for their pharmacokinetic study. Hereby, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid-liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as internal standard (IS), while solid phase extraction was adopted for sample preparation of BSP using prednisolone as IS. The chromatographic separation was performed on a Hypurity C18 column (150 mm×2.1 mm, 5 μm) for BOH, BDP, B21P and B17P, and a Luna C18 (2) column (150 mm×2.0 mm, 5 μm) for BSP. Electrospray ionization interfaced with positive multiple reaction monitoring (MRM) scan mode was used for mass spectrometric detection. The standard calibration curves were linear within the range of 2.525 × 10(-9)-403.9 × 10(-9) mol·dm(-3) for BSP, 0.125 × 10(-9)-55.81 × 10(-9) mol·dm(-3) for BDP, 0.278 × 10(-9)-74.95 × 10(-9) mol·dm(-3) for BOH, 0.098 × 10(-9)-4.688 × 10(-9) mol·dm(-3) for B17P and 0.226 × 10(-9)-5.411 × 10(-9) mol·dm(-3) for B21P, respectively. The validated method was successfully applied to a bioequivalence study in 23 healthy subjects after they were injected with this compound medicine BSP and BDP.

  14. Adesão ao uso de corticóide inalatório na asma: taxas relatadas pelos responsáveis e mensuradas pela farmácia Compliance with inhaled corticosteroid treatment: rates reported by guardians and measured by the pharmacy

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    Laura M. L. B. F. Lasmar


    Full Text Available OBJETIVO: A morbidade associada à asma é elevada, principalmente nos países em desenvolvimento, e as falhas na adesão ao uso de corticóide inalatório contribuem para esta elevação. Este estudo objetiva comparar as taxas de adesão ao uso de beclometasona relatadas pelos responsáveis e as mensuradas pelos registros de dispensação farmacêutica do medicamento. MÉTODOS: Foi realizado um estudo de coorte concorrente com duração de 12 meses, do qual participaram 106 crianças e adolescentes asmáticos, selecionados aleatoriamente. Através da regressão linear, as taxas de adesão relatadas pelos responsáveis e pelos registros de dispensação da farmácia do serviço foram correlacionadas, quadrimestralmente, a partir da admissão no estudo. RESULTADOS: As taxas de adesão relatadas pelos pais e/ou responsáveis foram sempre superiores (p OBJECTIVE: There is elevated morbidity associated with asthma, particularly in developing countries, and failure to comply with inhaled corticosteroid treatment contributes to this morbidity. The objective of this study is to compare rates of compliance with beclomethasone treatment reported by parents or guardians with those measured by pharmacy dispensing records. METHODS: A concurrent cohort study of 12 months' duration was carried out, enrolling 106 asthmatic children and adolescents, selected at random. Linear regression was used to compare rates of compliance reported by parents or guardians with the pharmacy dispensing records at the service, every 4 months after enrollment on the study. RESULTS: Compliance rates reported by parents and/or guardians were always higher (p < 0.001 and exhibited a weak correlation with pharmacy records during the period studied; fourth (r = 0.37 and twelfth (r = 0.31 months of follow-up. CONCLUSIONS: The rates of compliance reported by parents were overestimated during all study periods. The compliance rates of children with asthma should also be monitored by

  15. Study of efficacy of inhaled corticosteriods in chronic obstructive pulmonary disease%吸入糖皮质激素对慢性阻塞性肺疾病的抗炎效应

    Institute of Scientific and Technical Information of China (English)

    欧阳若芸; 陈平; 彭红


    Objective:To determine whether patients with COPD have favorable responses to inhaled corticosteroids (ICS). Methods: A randomized, placebo-controlled and single-blind trail of inhaled beclomethasone dipropionate (BDP 1000 μg daily for 6 weeks) was carried out in 30 patients with stable COPD. Before and after therapy,score of clinical symptoms and score of quality of life were recorded, spirometry and levels of endothelin-1 (ET-l) in plasma and induced sputum were measured, and cytologic examination in induced sputum was taken in. Results: Compared with the placebo-group after treatment, the BDP group showed significant improvement in symptom score (P <0.05) and FEV1 (P <0.01), but not quality of life (P >0.05); and reduction in the number of all cells (246+42)× 1O8/L vs (225+33) ×108/L, P <0.01), neutrophil propo tion (75.6±6.7)% vs (71.4+6.5)%, P <0.01) in induced sputum. The concentrations of ET-1 in plasma and induced sputum did not change significantly in both groups (P >0.05).Conclusions: The study suggests that the treatment with inhaled corticosteroids (1000 μg daily for 6 weeks) can improve clinical symptoms and pulmonary function, decrease inflammatory cells in airway in patients with stable COPD.%目的研究中等剂量二丙酸氯地米松(BDP)短疗程吸入治疗稳定期慢性阻塞性肺部疾病(COPD)是否有疗效.方法按照随机、对照、单盲的设计,30例稳定期COPD患者分类两组,分别予(1000BDPμg/d)与安慰剂吸入治疗6周,治疗前后测定肺功能一秒钟用力呼气容积(FEV1)、血浆内皮素(ET-1)的浓度,诱导痰细胞总数,中性粒细胞(PMN)分类及ET-1浓度,并记录临床症状记分,生活质量记分.结果27例完成实验,治疗组14例临床症状改善(治疗前4.3±1.2分,治疗后3.2±1.4分,P<0.05);FEV1提高显著(治疗前2.03±0.45 L,治疗后2.24±031 L,P<0.01);诱导痰中细胞总数治疗前:(246±42)×108/L治L,后:(225±33)×108/L,P<0.01),

  16. Pico do fluxo expiratório no acompanhamento de crianças asmáticas Peak expiratory flow monitoring in asthmatic children

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    Ana Cristina C. F. Fonseca


    Full Text Available OBJETIVO: Correlacionar as medidas de volume expiratório forçado no primeiro segundo (VEF1, pico do fluxo expiratório (PFE e parâmetros clínicos em crianças com asma moderada a grave. MÉTODOS: Trata-se de um estudo de coorte não concorrente, realizado em ambulatório de pneumologia pediátrica, em Belo Horizonte, MG, de março a outubro de 2002. Participaram do estudo crianças entre 5 e 16 anos, com asma persistente, em uso de beclometasona na dosagem mínima de 500 mcg/dia, com sintomas controlados há pelo menos 3 meses. Foram selecionados 75 pacientes (96,1% de forma aleatória simples, os quais foram acompanhados durante 3 meses, sendo avaliados o escore clínico e as provas de função pulmonar (PFE e VEF1. Os resultados foram analisados através da regressão linear de Pearson. RESULTADOS: Entre os valores absolutos e percentuais do PFE e o escore clínico, a correlação foi negativa e muito próxima a zero, o que significa uma correlação fraca, sem significância estatística. O mesmo se observa entre VEF1 e escore clínico. A correlação entre VEF1 e PFE apresentou valor positivo e com significância estatística (p = 0,000. CONCLUSÕES: Como o melhor parâmetro para avaliar obstrução de vias aéreas é o VEF1, o encontro de correlação positiva entre este e os valores absolutos do PFE reforça a importância do seu uso e permite recomendar a mensuração do PFE no manejo das crianças asmáticas, sobretudo nos casos graves.OBJECTIVE:To correlate forced expiratory volume in 1 second (VEF1 and peak expiratory flow (PEF with clinical parameters in children with moderate and severe asthma. METHODS: This was a non-concurrent cohort study, carried out at a pediatric pneumology clinic, in Belo Horizonte, MG, Brazil, between March and October 2002. The study enrolled children aged 5 to 16 years, with persistent asthma, being treated with a minimum of 500 mcg/day beclomethasone, and with symptoms under control for at least 3


    Directory of Open Access Journals (Sweden)

    Cesar Rente Ferreira


    sulfate (27%, beclomethasone (33.8% and ibuprofen (41.9%. The drugs that showed the greatest variation among the prices charged were: propranolol (97.1%, hydrochlorothiazide (96.4% and glibenclamide (95.0%, while the least variable were salbutamol (30.8% and trimethoprim-sulfamethoxazole (30.2%. Generic drugs, which were half (10 of those assessed, had the lowest prices. The indicators of access, referring to the ability of patients to acquire drugs for the treatment of major diseases at the primary health care level, showed that no establishment stocked all 20 essential drugs and that wide variations existed in their prices, undermining their availability to drug users, whose only sources are pharmacies and drugstores. These data demonstrate the importance of the popular pharmacy to improve the access to medicines, by lowering the cost and increasing the availability of the items selected for the National List of Essential Drugs (RENAME. Keywords: Drug Price. Economics, Pharmaceutical. Drugs, Generic. Pharmacoepidemiology.

  18. HIPERINFECCIÓN POR STRONGYLOIDES EN ANCIANO CON EPOC Strongyloides hyperinfection in elderly patient with COPD

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    Análida Elizabeth Pinilla-Roa


    Full Text Available Se presenta un caso de un hombre de 81 años natural de zona rural, agricultor, recolector de café 50 años atrás y jardinero por 22 años en Bogotá. Consultó por dolor abdominal de 10 días de evolución, localizado hacia mesogastrio y epigastrio. Además, disnea, tos productiva. Antecedentes: enfermedad pulmonar obstructiva crónica, cor pulmonale, fumador de 25 paquetes /año, había recibido prednisona oral y beclometasona inhalada en diversas ocasiones incluso en la última hospitalización. En el examen físico presentó signos de desnutrición, taquicardia, taquipnea; estertores en base del hemitórax derecho; abdomen: blando, depresible con dolor a la palpación profunda en epigastrio e hipocondrio derecho. Ingresó con síndrome de respuesta inflamatoria sistémica por taquicardia, taquipnea, leucocitosis 37.600 y eosinofilia 52-60%, Ig E: 180 UI/ ml. Se evidenciaron larvas rabditiformes de Strongyloides stercoralis en esputo y materia fecal. La radiografía de tórax mostró derrame pleural derecho, la ecografía hepática fue normal, la endoscopia de vías digestivas altas evidenció gastritis y duodenitis. Se inició tratamiento con ivermectina 200 mg/ Kg/dosis, con seguimiento clínico y de laboratorio con evolución clínica satisfactoria.The case is presented of an 81-years old man from a rural area who had been a farmer, a coffee harvester 50 years beforehand and a gardener in Bogotá for 22 years. He consulted because of abdominal pain having 10 days’ evolution, localized towards the mesogastrium and epigastrium. He was also suffering from dyspnoea and productive cough. Background: chronic obstructive pulmonary disease, smoking 25 packets/year, he had received oral prednisone and inhaled beclomethasone on occasions, including during his last hospitalization. Physical examination revealed signs of undernourishment, tachycardia, tachypnoea; stertors at the base of the right hemithorax; abdomen: soft, depressible with pain on