An Enhanced Understanding of the Powder Bed Fusion-Laser Beam Processing of Mg-Y-Nd-Zr (WE43) Alloy through Thermodynamic Modeling and Experimental Characterization.

Powder Bed Fusion-Laser Beam (PBF-LB) processing of magnesium (Mg) alloys is gaining increasing attention due to the possibility of producing complex biodegradable implants for improved healing of large bone defects. However, the understanding of the correlation between the PBF-LB process parameters and the microstructure formed in Mg alloys remains limited. Thus, the purpose of this study was to enhance the understanding of the effect of the PBF-LB process parameters on the microstructure of Mg alloys by investigating the applicability of computational thermodynamic modelling and verifying the results experimentally.

First-in-human phase 1 dose-escalation study of CAN04, a first-in-class interleukin-1 receptor accessory protein (IL1RAP) antibody in patients with solid tumours.

Background: Interleukin-1 (IL-1) signalling is involved in various protumoural processes including proliferation, immune evasion, metastasis and chemoresistance. CAN04 is a first-in-class monoclonal antibody that binds IL-1 receptor accessory protein (IL1RAP), required for IL-1 signalling. In this first-in-human phase 1 study, we assessed safety, recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of CAN04 monotherapy.

Relative systemic availability of budesonide in patients with asthma after inhalation from two dry powder inhalers.

Background: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI-A 200 microg) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI-B). Budesonide DPI-B is available in two strengths (90 microg, 180 microg).

Objective: To compare the relative rate and extent of the systemic availability of budesonide inhaled via DPI-A and DPI-B and test for systemic absorption bioequivalence.

Evidence of the in vivo esterification of budesonide in human airways.

Aims: Budesonide, unlike fluticasone propionate, undergoes fatty acid esterification in the lungs, and there is a need to characterize fully the distribution and fate of the two drugs after inhalation in humans.

Methods: This open-label, randomized study was performed in adults undergoing whole lung or lobar resection resulting from lung cancer. Patients were given single 1000-mug doses of both budesonide and fluticasone propionate via dry powder inhalers before surgery.

Exposure of infants to budesonide through breast milk of asthmatic mothers.

Background: Maintenance treatment with inhaled corticosteroids is often required for asthmatic nursing women. Data on the transfer of inhaled corticosteroids from plasma to breast milk and the subsequent exposure of the breast-feeding infant has been unavailable.

Objective: We sought to assess budesonide concentrations in milk and plasma of asthmatic nursing women receiving maintenance treatment with the Pulmicort Turbuhaler and estimate the exposure of their breast-fed infants.

Effects of topical formoterol alone and in combination with budesonide in a pollen season model of allergic rhinitis.

Background: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma exudation effects. While available data suggest no or only marginal effects of beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether these drugs may add to the efficacy of anti-rhinitis drugs.

Objective: To examine effects of a beta(2)-agonist, alone and in combination with an intranasal glucocorticosteroid, on symptoms and signs of allergic rhinitis.

Degree of throat deposition can explain the variability in lung deposition of inhaled drugs.

Inhalation is a mainstay for treatment of asthma, and lung deposition can be seen as a surrogate marker for the ensuing clinical effects. Not only absolute lung deposition, but also its variability is of interest, as it indicates the range of expected lung deposition in an individual patient when prescribing the drug and the expected day-to-day variability when using it. A literature survey found 71 studies with relevant information on lung deposition and its variability.

Idealhalers or realhalers? A comparison of Diskus and Turbuhaler.

Medication for the treatment of asthma and chronic obstructive pulmonary disease should be given locally by inhalation. There is, however, no such thing as an ideal inhaler, or 'Idealhaler', which has all desired properties with no drawbacks. In this short review, we have compared the relative merits of the two most commonly used dry powder inhalers -- Turbuhaler and Diskus.

Factors guiding the choice of delivery device for inhaled corticosteroids in the long-term management of stable asthma and COPD: focus on budesonide.

Inhaled corticosteroids (ICSs) have become the mainstay of chronic controller therapy to treat airways inflammation in asthma and to reduce exacerbations in chronic obstructive pulmonary disease. An array of ICSs are now available that are aerosolized by a range of delivery systems. Such devices include pressurized (or propellant) metered-dose inhalers (pMDIs), pMDIs plus valved holding chambers or spacers, breath-actuated inhalers, and nebulizers.

Drug disposition analysis: a comparison between budesonide and fluticasone.

The characterisation of distribution and elimination properties of a drug is usually done using parameters like clearance and distributional volumes. To refine this characterisation, in this paper, we use drug disposition analysis to compare the distribution and elimination of the two glucocorticosteroids budesonide and fluticasone propionate, known to differ in this respect. This gives a more detailed description of the well known differences in distributional volumes using concepts like mean residence time and fraction of dose outside the central compartment.

Systemic availability and lung deposition of budesonide via three different nebulizers in adults.

Background: Budesonide is an inhaled corticosteroid widely used in the treatment of asthma. The local and systemic availability of budesonide has been determined in adults via pressurized metered-dose inhaler and dry-powder inhaler.

Objective: To estimate lung deposition and systemic availability of budesonide inhalation suspension in healthy adults.

Pharmacokinetics and systemic activity of fluticasone via Diskus and pMDI, and of budesonide via Turbuhaler.

Aims: To determine the basal pharmacokinetics, lung uptake and plasma cortisol suppression for two commonly prescribed inhaled corticosteroids.

Methods: Twenty-one subjects (13 healthy and 8 mild asthmatic patients) received fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus and budesonide via Turbuhaler, 1000 microg twice daily for 7 days. Intravenous doses (200 microg) of both compounds were used as references.

A randomized controlled assessment of the effects of different dosing regimens of budesonide on the HPA-axis in healthy subjects.

Aims: To investigate the effect on the hypothalamo-pituitary-adrenal (HPA) axis of treatment with budesonide, 400 microg once daily, morning or evening, or 200 microg twice daily, and 800 microg twice daily via Turbuhaler in a randomized, placebo-controlled, double-blind, double-dummy crossover study.

Methods: Healthy men received budesonide, 400 microg in the morning (08.00-09.

Lung deposition of inhaled drugs increases with age.

Budesonide plasma concentrations after inhalation of a fixed dose of the drug from a pressurized metered dose inhaler (pMDI) with spacer (Nebuchamber) were compared in young children and adults: 26 patients with mild asthma comprising 8 children 2-3 yr, 8 children 4-6 yr, and 10 adults 20-41 yr. Budesonide 2 x 200 microg was given by pMDI via Nebuchamber with mouthpiece and noseclip. Children of 2-3 yr used a facemask.

A randomized controlled assessment of the systemic activity of budesonide when given once or twice daily via Turbuhaler.

Objective: To compare the effects on the hypothalamo-pituitary-adrenal (HPA) axis of budesonide, delivered via Turbuhaler at doses of 800 microg once daily in the morning or evening or 400 microg twice daily.

Methods: Healthy men (n = 24) received four treatments in random order: budesonide, 800 Fg in the morning and placebo in the evening; budesonide, 800 microg in the evening and placebo in the morning; budesonide, 400 microg in the morning and evening; placebo in the morning and evening. Each treatment was given for 1 week, with a 2-week washout period between treatments.

Systemic availability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder.

Aims: The present study was undertaken to determine the absolute systemic availability of budesonide from three different devices for nasal administration: pressurized aerosol, aqueous pump spray, and powder.

Methods: Sixteen healthy, non-smoking, volunteers participated in this open, randomized, and crossover study. All subjects received budesonide as an intravenous dose of 400 microg, and as three, single-dose, intranasal administrations: pressurized aerosol 800 microg, aqueous pump spray 400 microg, and powder 800 microg.

Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer.

The absolute systemic availability and pulmonary deposition of budesonide inhaled from a pressurized metered-dose inhaler (pMDI) attached to a Nebuhaler spacer was determined in 15 healthy subjects. The study was of an open cross-over design. Each subject randomly received three single doses of budesonide on separate days: 0.

The effects of static charge in spacer devices on glucocorticosteroid aerosol deposition in asthmatic patients.

Electrostatic charge in plastic spacer devices has been shown in vitro to reduce delivery of asthma medications intended for inhalation, but the effect of static charge on in vivo drug deposition is unknown. A six-way randomized crossover study was conducted in 10 mild asthmatic patients. Two plastic spacers (Nebuhaler and Volumatic) and one metal spacer (Nebuchamber) were tested.

Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: a dose-response study.

Background: As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects.

Objectives: This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 microg/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma.

Pharmacokinetics and systemic effects of inhaled fluticasone propionate in healthy subjects.

Aims: The present study was undertaken to see whether the difference in plasma cortisol suppression between single and repeated dosing of fluticasone propionate (FP) can be explained by systemic accumulation.

Methods: Twelve healthy subjects (six women) were given, in a crossover fashion, a single dose inhalation (1000 micrograms) of FP via Diskhaler and repeated inhalations (1000 micrograms twice daily) every 12 h during 7 days. There was a washout period of 2 weeks between the treatments.

Influence of inhaler systems on systemic availability, with focus on inhaled corticosteroids.

Local treatment of obstructive pulmonary diseases, such as asthma, is achieved by oral inhalation of the active substance. Drug deposited in the lung may then exert its effects locally before it is absorbed into the systemic circulation. The systemic availability of a drug is made up of the fraction deposited in the lung and the fraction deposited in the oropharynx, which is swallowed and absorbed from the gastrointestinal (GI) tract.

Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI.

The pulmonary and systemic availability of budesonide after inhalation from a dry powder inhaler, Turbuhaler, and from a pressurized metered-dose inhaler (P-MDI) were compared in healthy volunteers. Two different methods were used to assess pulmonary availability: 1) calculated from the systemic availability corrected for an oral availability of 13% (n = 24); and 2) after blocking of gastrointestinal absorption by administration of a charcoal suspension (n = 13). An intravenous infusion of budesonide was used as a reference.

Nasal distribution of budesonide inhaled via a powder inhaler.

The distribution pattern of budesonide in the nasal passages and lungs was investigated in 10 healthy subjects after nasal inhalation. The subjects inhaled drug powder, radiolabelled with 99mTc, at maximum flow rate (46.3 +/- 6.