Salbutamol Research Articles

Development of a highly sensitive time-resolved fluoroimmunoassay for the determination of trace salbutamol in environmental samples

Veterinary drug residues have become a major source of environmental pollutants. To monitor trace salbutamol (SAL) in the environment, a highly sensitive and reliable time-resolved fluoroimmunoassay (TRFIA) was developed. Under the optimum parameters, the half-maximal inhibition concentration (IC50) and the limit of detection (LOD, IC10) were determined to be 0.08 μg/L and 0.66 ng/L with a linear range (IC20 - IC80) of 0.0028–2.25 μg/L for SAL. The IC50 and LOD of the TRFIA improved approximately 5-fold and 31-fold, respectively, when compared with our previously reported ELISA data. When compared to most other conventional methods, the TRFIA also showed an excellent sensitivity and accuracy for the detection of SAL. Recoveries from 83.4 to 111.3% and standard deviations (RSDs) from 3.9 to 14.0% were observed in various environmental SAL-spiked samples, including river water, paddy water, livestock wastewater, vegetable field soil and rice paddy soil. In addition, the developed TRFIA showed largely consistent with analytic results from UPLC-MS/MS (R2 = 0.9825, n = 15). These results suggest that the proposed TRFIA can be applied as a sensitive and reliable monitoring method to detect trace SAL in environmental samples.

Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies

Tonsillectomy is a common pediatric procedure for the treatment of sleep-disordered breathing and chronic tonsillitis. Up to half of children having this procedure experience a perioperative respiratory adverse event. To determine whether inhaled albuterol sulfate (salbutamol sulfate) premedication decreases the risk of perioperative respiratory adverse events in children undergoing anesthesia for tonsillectomy. A randomized, triple-blind, placebo-controlled trial (the Reducing Anesthetic Complications in Children Undergoing Tonsillectomies [REACT] trial) was conducted at Perth Children's Hospital (formerly Princess Margaret Hospital for Children), the only tertiary pediatric hospital in Western Australia. Participants included 484 children aged 0 to 8 years who were undergoing anesthesia for tonsillectomy. The study was conducted between July 15, 2014, and May 18, 2017. Participants were randomized to receive either albuterol (2 actuations, 200 μg) or placebo before their surgery. Occurrence of perioperative respiratory adverse events (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing, and stridor) until discharge from the postanesthesia care unit. Of 484 randomized children (median [range] age, 5.6 [1.6-8.9] years; 285 [58.9%] boys), 479 data sets were available for intention-to-treat analysis. Perioperative respiratory adverse events occurred in 67 of 241 children (27.8%) receiving albuterol and 114 of 238 children (47.9%) receiving placebo. After adjusting for age, type of airway device, and severity of obstructive sleep apnea in a binary logistic regression model, the likelihood of perioperative respiratory adverse events remained significantly higher in the placebo group compared with the albuterol group (odds ratio, 2.8; 95% CI, 1.9-4.2; P < .001). Significant differences were seen in children receiving placebo vs albuterol in laryngospasm (28 [11.8%] vs 12 [5.0%]; P = .009), coughing (79 [33.2%] vs 27 [11.2%]; P < .001), and oxygen desaturation (54 [22.7%] vs 36 [14.9%]; P = .03). Albuterol premedication administered before tonsillectomy under general anesthesia in young children resulted in a clinically significant reduction in rates of perioperative respiratory adverse events compared with the rates in children who received placebo. Premedication with albuterol should be considered for children undergoing tonsillectomy. Australian New Zealand Clinical Trials Registry identifier: ACTRN12614000739617.

Contrasting photoreactivity of β2-adrenoceptor agonists Salbutamol and Terbutaline in the presence of humic substances

The photodegradation reactions of two typical β2-adrenoceptor agonists, salbutamol (SAL) and terbutaline (TBL), alone, and in the presence of Aldrich humic acid (AHA) or Suwannee River fulvic acid (SRFA) were investigated by steady-state photolysis experiments, laser flash photolysis (LFP), kinetic modeling and quantum calculation. AHA and SRFA (2–20 mgC L−1) accelerated the phototransformation of both SAL and TBL. For SAL, an inhibiting effect of oxygen on the photodegradation was observed that is fully consistent with the main involvement of excited triplet states of HS (3HS*). On the contrary, oxygen drastically enhanced the photodegradation of TBL showing that 3HS* were negligibly involved in the reaction. The involvement of singlet oxygen was also ruled out because of the low reaction rate constant measured between TBL and singlet oxygen. Quantum calculations were therefore performed to explore whether oxygenated radicals could through addition reactions explain the differences of reactivity of TBL and SAL in oxygen medium. Interestingly, calculations showed that in the presence of oxygen, the addition of phenoxyl on TBL led to the formation of adducts and to the loss of TBL while the same addition reaction on SAL partly regenerated the starting compound and at the end degraded SAL less efficiently. This study is of high relevance to understand the processes involved in SAL and TBL phototransformation and the photoreactivity of HS. Moreover, our findings suggest that TBL might be a promising probe molecule to delineate the role of oxygenated radicals.

Simultaneous determination of β-agonists by UHPLC coupled with electrochemical detection based on palladium nanoparticles modified BDD electrode

Palladium nanoparticles (PdNPs) modified boron-doped diamond (BDD) electrode was simply fabricated via electrodeposition technique for the sensitive electro-analysis of four β-agonist compounds, including terbutaline (TER), salbutamol (SAL), ractopamine (RAC), and clenbuterol (CLB) after a prior separation by ultra-high performance liquid chromatography (UHPLC). The separation was carried out using a reverse phase C18 column with gradient elution of appropriate proportion between methanol and phosphate buffer solution (PBS) pH7.0 at a flow rate of 1.0minmL−1. The following electrochemical detection (ECD) was accomplished by amperometric method with a detection potential of 1.0V vs Ag/AgCl. The modified BDD electrode, unlike other carbon-based electrodes used for β-agonists detection, typically showed the superior anti-fouling ability and provided excellent long-term stability, resulting in no complicated cleaning steps needed during each determination. The measurement of β-agonists using the PdNPs modified BDD electrode integrated with UHPLC showed a linear relationship in the range of 0.2 to 200μgmL−1 with detection limits of 0.04, 0.02, and 0.03μgmL−1 for TER, SAL, and RAC, respectively. Meanwhile, CLB displayed linearly in the range of 0.5 to 200μgmL−1 with a detection limit of 0.19μgmL−1. Moreover, this method was successfully applied to detect β-agonists in diverse samples, including swine feed, swine meat, and human urine with satisfied recoveries in the range from 80.5% to 110.0%. Reliability of this developed method was also validated with ultra-high performance liquid chromatography coupled with ultra-violet detection (UHPLC-UV), and the results showed highly quantitative agreement between the two methods. Therefore, the PdNPs modified BDD could be productively utilized as effective electrodes, with good electrocatalytic activity of PdNPs towards β-agonists oxidation and favorable anti-fouling performance of BDD. The simultaneous detection of four β-agonists by UHPLC-ECD exhibited good stability, acceptable reusability, high sensitivity and rapid analysis.

Sulfate radical induced degradation of β2-adrenoceptor agonists salbutamol and Terbutaline: Implication of halides, bicarbonate, and natural organic matter

The presence of inorganic ions and organic matter in natural water would cause unpredictable consequence on the oxidation efficiency and pathways of sulfate radical (SO4−) based advanced oxidation process (SR-AOPs). In this study, the impacts of water constituents, namely, halides (including chloride (Cl−) and bromide (Br−)), bicarbonate (HCO3−) and natural organic matter (NOM) on SO4− induced degradation of salbutamol (SAL) and terbutaline (TBL) were evaluated systematically. Our results indicated that chloride exhibited no effect on oxidation efficiencies of SAL and TBL, while Br−, HCO3− and NOM all showed inhibitory effects. Specifically, the detrimental effect of bromide was mainly attributed to the scavenging of SO4− to form the less reactive species, Br2−. By using laser flash photolysis (LFP), the second-order rate constants of Br2− with SAL and TBL were estimated to be 2.1 and 3.9 × 108 M−1 s−1, respectively, much smaller than those with SO4− (3.7 × 109 M−1 s−1 for SAL and 4.2 × 109 M−1 s−1 for TBL). Moreover, bromine addition products of SAL and TBL were detected in the presence of Br−, which were believed to be more toxic than the parent compounds. Similar to bromide, HCO3− could also quench SO4− to generate carbonate radical (CO3−), also less reactive than sulfate radical with SAL (4.8 × 107 M−1 s−1) and TBL (3.2 × 108 M−1 s−1). In the case of NOM, a light screening effect was regarded as the major factor responsible to the decrease of reaction rates, while sulfate radical scavenging played a very limited role. The present work would increase the awareness of secondary reactions during SR-AOPs, as more toxic products were generated in the case of bromide.

Investigation of the Quantity of Exhaled Aerosols Released into the Environment during Nebulisation.

Background: Secondary inhalation of medical aerosols is a significant occupational hazard in both clinical and homecare settings. Exposure to fugitive emissions generated during aerosol therapy increases the risk of the unnecessary inhalation of medication, as well as toxic side effects. Methods: This study examines fugitively-emitted aerosol emissions when nebulising albuterol sulphate, as a tracer aerosol, using two commercially available nebulisers in combination with an open or valved facemask or using a mouthpiece with and without a filter on the exhalation port. Each combination was connected to a breathing simulator during simulated adult breathing. The inhaled dose and residual mass were quantified using UV spectrophotometry. Time-varying fugitively-emitted aerosol concentrations and size distributions during nebulisation were recorded using aerodynamic particle sizers at two distances relative to the simulated patient. Different aerosol concentrations and size distributions were observed depending on the interface. Results: Within each nebuliser, the facemask combination had the highest time-averaged fugitively-emitted aerosol concentration, and values up to 0.072 ± 0.001 mg m−3 were recorded. The placement of a filter on the exhalation port of the mouthpiece yielded the lowest recorded concentrations. The mass median aerodynamic diameter of the fugitively-emitted aerosol was recorded as 0.890 ± 0.044 µm, lower the initially generated medical aerosol in the range of 2–5 µm. Conclusions: The results highlight the potential secondary inhalation of exhaled aerosols from commercially available nebuliser facemask/mouthpiece combinations. The results will aid in developing approaches to inform policy and best practices for risk mitigation from fugitive emissions.

Influence of salbutamol on the anticonvulsant potency of the antiepileptic drugs in the maximal electroshock-induced seizures in mice.

β2-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β2-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures. Seizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals' motor coordination and memory processes was also evaluated. Single SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β2-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals' motor performance and memory after both single and 7 days administration. Presented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β2-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.

Clinical effect of montelukast combined with budesonide in the treatment of children with cough variant asthma

Objective To explore the curative effect of montelukast combined with budesonide in the treatment of cough variant asthma in children, to provide guidance for clinical practice. Methods From March 2015 to March 2017, 90 children with cough variant asthma in the People's Hospital of Yanggu County were randomly divided into observation group(n=45) and control group(n=45) according to the digital table.The observation group was given budesonide combined with montelukast, while the control group was given budesonide combined with salbutamol sulfate.All patients were followed up for 3 months.The curative effect, cough relief time, cough disappearance time, incidence rate of adverse reaction and recurrence rate were compared between the two groups. Results The total effective rate of the observation group(95.56%) was significantly higher than 77.78% of the control group(P 0.05). The recurrence rate of the observation group (4.44%) was significantly lower than 17.78% of the control group(P<0.05). Conclusion It is feasible to treat cough variant asthma in children with montelukast combined with budesonide, and it is helpful to reduce recurrence. Key words: Montelukast; Budesonide; Children; Asthma, Variability; Salbutamol Sulfate

Preparation of salbutamol imprinted magnetic nanoparticles via boronate affinity oriented surface imprinting for the selective analysis of trace salbutamol residues.

Salbutamol (SAL) is one of the most widely abused feed additives in animal husbandry. Selective enrichment of SAL from complex biological samples is a key step for the analysis of SAL. Herein, we present SAL-imprinted magnetic nanoparticles (MNPs) as an ideal sorbent for selective enrichment of SAL. The SAL-imprinted MNPs were prepared according to the newly reported boronate affinity oriented surface imprinting. The prepared imprinted MNPs exhibited several significant advantages, such as excellent selectivity towards SAL, superb tolerance to interferences, fast binding equilibrium and easy manipulation, which made the obtained imprinted MNPs an ideal sorbent for selective enrichment. The feasibility of SAL-imprinted MNPs for real samples was well demonstrated by the analysis of trace SAL in pig liver. Because of their highly desirable properties, the SAL-imprinted MNPs could find more applications in the analysis of SAL.

Simultaneous determination of β-agonists on hexagonal boron nitride nanosheets/multi-walled carbon nanotubes nanocomposite modified glassy carbon electrode

β-Agonists are illegally consumed in various products such as food and animal and effect the nutrition distribution owing to change of body fat. In addition, they result in acute poisoning and several symptoms such as muscular tremors and nervousness. A new electrochemical approach based on two-dimensional hexagonal boron nitride (2D-hBN) nanosheets decorated functionalized multi-walled carbon nanotubes (f-MWCNTs) was presented for simultaneous determination of β-agonists such as phenylethanolamine A (PEA), clenbuterol (CLE), ractopamine (RAC) and salbutamol (SAL) in urine samples. X-ray diffraction (XRD) method, Raman spectroscopy, scanning electron microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used characterizations of nanomaterials. After that, 2D-hBN/f-MWCNTs nanocomposite modified glassy carbon electrode (GCE) was prepared for simultaneous determination of β-agonists. 1.0 × 10−12–1.0 × 10−8 M and 1.0 × 10−13 M were founded as the linearity range and the detection limit (LOD) for PEA, CLE, RAC and SAL. Finally, the prepared electrochemical sensor was used for urine sample analysis in presence of ascorbic acid (AA) and uric acid (UA).

Hypofibrinogenemia in Patient with Extended Exposure to Argatroban Therapy

A 42 year old female with past medical history of asthma and recent admission for Alprazolam overdose presented to our hospital with dyspnea and generalized weakness.. She was noted by paramedics to be hypoxic, hypotensive and bradycardic, and she was intubated in the field prior to arrival.. Medication prior to admission, Albuterol HFA. Patient had no known drug allergies. On presentation to the emergency department, patient appeared critically ill, hypotensive to 74/50 , hypoxic with oxygen saturation of 60%, heart rate of 137 BPM, respiratory rate 15/min, temp 99 F, and unresponsive to verbal stimuli. Endotrachial tube placement was confirmed using laryngoscope. Whilein ED, patient went into Pulseless Electrical activity state and CPR was started immediately. She was given one round of Epinephrine with return of spontaneous circulation after 3 minutes.Bedside transthoracic echo suggestive of right heart strain, patient was given Tenecteplase given high risk of Pulmonary embolism. She was then transferred to the Intensive care unit and was started on pressure support.. Initial Chest CT angiogram showed no signs of pulmonary embolism. Pertinent laboratory values at admission were, serum Creatinine 1.28 mg/dl , WBC 14 K/mcl, HGB 12/4 g/dl, Platelet count 186 K/mcl, PT 12.4 sec, INR 1.1, APTT 29.9 sec, Arterial blood gas with PH 7.039, PCO2 70.9 mmhg, PO2 35.9 mmhg, HCO3 18.2 mmol/l and Lactate 11.0 mmol/l. Hepatic function panel showing Albumin 3.7 gm/dl, Total protein 7.2 gm/dl, Total Bilirubin 0.6 mg/dl, Direct Bilirubin 0.1 ml/dl, ALK Phos 95 U/L, ALT 58 U/L, AST 73 U/L.Patient respiratory status improved and was extubated on day 2, she was transferred to step down unit. Patient initially was on DVT prophylaxis dose of LMWH 5000 unit at bed time. However on day 5 laboratory values were notable for a drop in Platelets to 37 K/mcl, suspicion that patient developed HIT as 4T score of 6 ( high probability of of HIT 64%) which was confirmed with positive Serotonin releasing essay. On day 6 post admission, patient reported right calf pain, venous duplex studyof the lower extremity was performed showing lack of compressibility in right proximal, middle and distal superficial femoral veins consistent deep venous thrombosis . A lung perfusion scan was done showing high probability of pulmonary thromboembolic process. Administration of Argatroban was initiated at 2 mcg/kg/min IV titrated to goal of APTT 1.5-3x of baseline up 100 sec. Subsequent daily labs showing continuous drop in Fibrinogen levels(persistent <35 mg/dl, Normal 233-394) with appropriate increase in APTT values ( therapeutic goal of 45-90) and normal PT, INR values.Subsequently, patient was receiving fresh frozen plasma twice daily. After careful review of the case with hematology consult, the drop in Fibrinogen levels was noted to be corresponding with he 12 days of Argatroban administration, so decision was made to stop Argatroban and switch to fondaparinaux. Fibrinogen values returned to normal within 1 day of discontinuation of Argatroban therapy (bridging to W arfarin), raising the concern for Argatroban induced hypofibrinogenemia. DisclosuresNo relevant conflicts of interest to declare.

The crucial role of leucine concentration on spray dried mannitol-leucine as a single carrier to enhance the aerosolization performance of Albuterol sulfate

Generally, DPI formulations show low fine particle fraction (FPF) due to poor detachment of drug particles from carrier during inhalation. l-Leucine, with varying concentrations (ranging from 0 to 10% w/w), were introduced into a 60%w/v mannitol solution where the solutions were then spray dried to achieve a new processed carrier. The spray dried samples were blended with Albuterol sulfate to determine the efficacy of their aerosolization performance. Analyzing each formulation was completed via the implementation of numerous analytical techniques such as particle size distribution analysis via laser diffraction, differential scanning calorimetry (DSC), scanning electron microscope (SEM), powder X-Ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy, and an in vitro deposition study. It was shown the concentration of leucine in spray dried is really crucial to achieve the highest FPF possible. The highest FPF was obtained for the samples containing 10% w/w leucine which was 52.96 ± 5.21%. It was interesting to note that the presence of leucine produced different polymorphic forms for mannitol. Moreover, through this study, the authors were able to conclude that mannitol can serve as an alternative carrier in DPI formulations containing Albuterol sulfate tailored for lactose intolerant patients.

Development of a novel digital breath-activated inhaler: Initial particle size characterization and clinical testing

BackgroundDelivery of inhaled respiratory medications have been associated with variable delivery of drug due to errors in device operations and have not been designed to monitor true delivery of medication. A fully digital breath-activated inhaled (DBAI) delivery platform has been developed with integrated firmware and software to address these limitations. Methodsthe device was designed to produce similar aerosol particle output to a marketed albuterol MDI and to the albuterol/ipratropium combination in a soft mist inhaler (SMI). Cascade impactor studies were conducted to demonstrate comparable aerodynamic particle size distribution (APSD) metrics. Efficacy was evaluated by pharmacodynamic studies involving spirometry in two separate protocols with adult subjects having COPD (albuterol DBAI vs. albuterol MDI – Study A, albuterol/ipratropium DBAI single arm – Study B). ResultsThe total emitted doses (TED) were 81.9 ± 10.3, 109.3 ± 15.0 and 121.9 ± 7.0 μg/actuation for the DBAI, SMI and MDI respectively, and the fine (respirable) particle doses (FPD) were 56.2 ± 6.0, 61.7 ± 5.5 and 79.4 ± 2.7 μg/actuation. MMADs for albuterol sulfate were 1.93 ± 0.11, 1.75 ± 0.19, and 2.65 ± 0.05 μm for the DBAI, Respimat soft mist inhaler (SMI) and MDI respectively. The corresponding GSDs were 1.96 ± 0.16, 2.79 ± 0.25, and 1.48 ± 0.02 μm. The corresponding respirable fractions were 68.7 ± 3.2%, 57.3 ± 10.5%, and 65.2 ± 2.4%. Spirometric study A enrolled 23 subjects (age 64 ± 7.3 years, 39% male, FEV1 45 ± 14% predicted). Study B enrolled 23 subjects (age 65 ± 8.6 years, 43% male, FEV1 47 ± 10% predicted). For Study A, FEV1 at 20 min post-dose improved by 120 (167) mL (p = 0.002) for the DBAI device and 109 (183) mL (p = 0.008) for the MDI device (p = 0.86 for between group differences). For Study B, FEV1 (20 min post-dose) improved by 216 (126) mL (p < 0.001). ConclusionThe DBAI generated highly respirable aerosols containing albuterol sulfate that were similar to the MDI and SMI in respirable fraction but lower in dose. Subsequent pharmacodynamic studies delivering albuterol sulfate alone and in combination with ipratropium bromide confirmed similar responses for the DBAI compared with the other inhalers, which could possibly be related to a response ceiling. The DBAI breath-activated capability combined with the ability to monitor actual delivery of medication may improve effectiveness by overcoming patient miscoordination.

Simultaneous determination of salbutamol and propranolol in biological fluid samples using an electrochemical sensor based on functionalized-graphene, ionic liquid and silver nanoparticles

A simple, rapid, and low-cost electroanalytical method was developed using a glassy carbon electrode modified with functionalized-graphene (FG), ionic liquid (IL) and silver nanoparticles (AgNPs) for simultaneous detection of salbutamol (SAL) and propranolol (PRO). The electrochemical behaviour of the electrodes was investigated by cyclic voltammetry and square wave voltammetry (SWV) under optimised conditions. Using SWV, the AgNP-IL-FG-NF/GCE sensor showed a linear response from 79 nmol L−1 to 2.9 μmol L−1 for SAL and from 0.1 to 2.9 μmol L−1 for PRO with limits of detection of 13 and 17 nmol L−1 for SAL and PRO, respectively. The proposed sensor showed good stability, repeatability and reproducibility, and was applied successfully to the simultaneous determination of SAL and PRO in biological fluid samples. The proposed method proved to be excellent, being therefore a reliable alternative method for the simultaneous determination of SAL and PRO.

Efficacy of atomized budesonide treating neonatal bronchopulmonary dysplasia after discharge from hospital

Objective To investigate the effects of atomized budesonide on neonatal bronchopulmonary dysplasia after discharge from hospital to 6 months of gestational age correction. Methods Analyse clinical data of fifty children with BPD, observe the effects of atomized budesonide (0.5mg inhaled q12h, at least 4weeks, course(15.4±6.16)weeks.When wheezing or dyspnea occurred: 1mg of budesonide and 1.25ml of albuterol and ipratropium bromide inhaled q12h, 2~4weeks.When respiratory frequency, heart rate and blood oxygen saturation reached normal, three concave improved obviously, lung rale disappeared, gradually reduce to no treatment)improving the clinical symptoms of children with BPD in 6 months after discharge, and observe the effects of atomized budesonide on reducing respiratory tract infection(including upper respiratory tract infection, pneumonia, wheezing and hospitalization). Results Through budesonide aerosol therapy, respiratory frequency and heart rate of children with BPD could be reduced, blood oxygen saturation could be elevated , and three concave could be improved at corrected gestational age of 3 months and 6 months.(P 0.05). Conclusion The treatment of budesonide atomization can improve the clinical symptoms of children with BPD after discharge from hospital to 6 months of gestational age correction, improve oxygen and shorten the time of oxygen inhalation after hospital, cannot reduce the incidence of respiratory infection. Key words: Preterm infant; Bronchopulmonary dysplasia; Budesonide; Efficacy

Effects of Acute Salbutamol Intake on Peripheral and Central Fatigue in Trained Men.

Ergogenic effect in physically active subjects has been reported after acute salbutamol (SAL) intake. β2-Agonists have potential stimulant effects within the central nervous system that could be involved in this ergogenic effect. We hypothesized that acute SAL intake would induce changes in cerebral responses during exercise, with significant improvement in cerebral oxygenation and voluntary activation (VA) contributing to an increase in muscle performance. Fourteen trained male subjects (25 ± 5 yr) performed repeated isometric knee extensions until task failure (TF) after 4 mg (oral) SAL, 800 μg (inhaled) SAL, or placebo intake. VA, corticospinal excitability, and inhibition assessed by transcranial magnetic stimulation and changes in hemoglobin concentrations assessed by near-infrared spectroscopy were measured before and during the fatiguing task. SAL had no significant effect both at rest and during exercise on prefrontal cortex oxygenation (e.g., changes in oxyhemoglobin concentration at TF: 11.4 ± 11.1 (4 mg SAL) vs 10.4 ± 10.6 (800 μg SAL) vs 10.8 ± 8.1 μmol (placebo); P = 0.314) and neuromuscular function (e.g., VA measured by TMS at TF: 90.2% ± 6.6% vs 92.6% ± 5.0% vs 90.1% ± 7.0%; P = 0.760). SAL had no effect on the number of contractions until TF (95 ± 51 vs 100 ± 52 vs 93 ± 47; P = 0.629). These results indicate that acute SAL intake had no effect on central and peripheral mechanisms of neuromuscular fatigue and did not improve quadriceps endurance.

Effects of Formulation Variables on Lung Dosimetry of Albuterol Sulfate Suspension and Beclomethasone Dipropionate Solution Metered Dose Inhalers

The performance of pressurized metered dose inhalers (MDIs) is affected by formulation and device variables that impact delivered dose, aerodynamic particle size distribution, and consequently lung deposition and therapeutic effect. Specific formulation variables of relevance to two commercially available products-Proventil® HFA [albuterol sulfate (AS) suspension] and Qvar® [beclomethasone dipropionate (BDP) solution]-were evaluated to determine their influence on key performance attributes measured experimentally with in vitro cascade impaction studies. These commercial MDIs, utilized as model systems, provided mid-points for a design of experiments (DoE) plan to manufacture multiple suspension and solution MDI formulations. The experimental results were utilized as input variables in a computational dosimetry model to predict the effects of MDI formulation variables on lung deposition. For the BDP solution DoE MDIs, increased concentrations of surfactant oleic acid (0-2% w/w) increased lung deposition from 24 to 46%, whereas changes in concentration of the cosolvent ethanol (7-9% w/w) had no effect on lung deposition. For the AS suspension DoE MDIs, changes in oleic acid concentration (0.005-0.25% w/w) did not have significant effects on lung deposition, whereas lung deposition decreased from 48 to 26% as ethanol concentration increased from 2 to 20% w/w, and changes in micronized drug volumetric median particle size distribution (X50, 1.4-2.5μm) increased deposition in the tracheobronchial airways from 5 to 11%. A direct correlation was observed between fine particle fraction and predicted lung deposition. These results demonstrate the value of using dosimetry models to further explore relationships between performance variables and lung deposition.

Mixing of low-dose cohesive drug and overcoming of pre-blending step using a new gentle-wing high-shear mixer granulator

The objective of this study was to examine the influence of drug amount and mixing time on the homogeneity and content uniformity of a low-dose drug formulation during the dry mixing step using a new gentle-wing high-shear mixer. Moreover, the study investigated the influence of drug incorporation mode on the content uniformity of tablets manufactured by different methods. Albuterol sulfate was selected as a model drug and was blended with the other excipients at two different levels, 1% w/w and 5% w/w at impeller speed of 300 rpm and chopper speed of 3000 rpm for 30 min. Utilizing a 1 ml unit side-sampling thief probe, triplicate samples were taken from nine different positions in the mixer bowl at selected time points. Two methods were used for manufacturing of tablets, direct compression and wet granulation. The produced tablets were sampled at the beginning, middle, and end of the compression cycle. An analysis of variance analysis indicated the significant effect (p < .05) of drug amount on the content uniformity of the powder blend and the corresponding tablets. For 1% w/w and 5% w/w formulations, incorporation of the drug in the granulating fluid provided tablets with excellent content uniformity and very low relative standard deviation (∼0.61%) during the whole tableting cycle compared to direct compression and granulation method with dry incorporation mode of the drug. Overall, gentle-wing mixer is a good candidate for mixing of low-dose cohesive drug and provides tablets with acceptable content uniformity with no need for pre-blending step.

Protection against severe hypokalemia but impaired cardiac repolarization after intense rowing exercise in healthy humans receiving salbutamol.

Intense exercise induces pronounced hyperkalemia, followed by transient hypokalemia in recovery. We investigated whether the β2 agonist salbutamol attenuated the exercise hyperkalemia and exacerbated the postexercise hypokalemia, and whether hypokalemia was associated with impaired cardiac repolarization (QT hysteresis). Eleven healthy adults participated in a randomized, counterbalanced, double-blind trial receiving either 1,000 µg salbutamol (SAL) or placebo (PLAC) by inhalation. Arterial plasma potassium concentration ([K+]a) was measured at rest, during 3 min of intense rowing exercise, and during 60 min of recovery. QT hysteresis was calculated from ECG ( n = 8). [K+]a increased above baseline during exercise (rest, 3.72 ± 0.7 vs. end-exercise, 6.81 ± 1.4 mM, P < 0.001, mean ± SD) and decreased rapidly during early recovery to below baseline; restoration was incomplete at 60 min postexercise ( P < 0.05). [K+]a was less during SAL than PLAC (4.39 ± 0.13 vs. 4.73 ± 0.19 mM, pooled across all times, P = 0.001, treatment main effect). [K+]a was lower after SAL than PLAC, from 2 min preexercise until 2.5 min during exercise, and at 50 and 60 min postexercise ( P < 0.05). The postexercise decline in [K+]a was correlated with QT hysteresis ( r = 0.343, n = 112, pooled data, P = 0.001). Therefore, the decrease in [K+]a from end-exercise by ~4 mM was associated with reduced QT hysteresis by ~75 ms. Although salbutamol lowered [K+]a during exercise, no additive hypokalemic effects occurred in early recovery, suggesting there may be a protective mechanism against severe or prolonged hypokalemia after exercise when treated by salbutamol. This is important because postexercise hypokalemia impaired cardiac repolarization, which could potentially trigger arrhythmias and sudden cardiac death in susceptible individuals with preexisting hypokalemia and/or heart disease. NEW & NOTEWORTHY Intense rowing exercise induced a marked increase in arterial potassium, followed by a pronounced decline to hypokalemic levels. The β2 agonist salbutamol lowered potassium during exercise and late recovery but not during early postexercise, suggesting a protective effect against severe hypokalemia. The decreased potassium in recovery was associated with impaired cardiac QT hysteresis, suggesting a link between postexercise potassium and the heart, with implications for increased risk of cardiac arrhythmias and, potentially, sudden cardiac death.

Continuous Albuterol Therapy in Pediatric Acute Care: Safe and Efficacious Management Outside the ICU

There is little data to support the use of continuous nebulized albuterol (CNA) in the non-ICU or non-ER setting for pediatric patients with status asthmaticus; many pediatric hospitals admit these patients to a critical care setting. A recent 2014 study demonstrated low rates of adverse outcomes with the administration of CNA on the acute care (general inpatient) unit; however, additional outcomes have not been previously described. We sought to determine if there were …