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PubMed1992

Metered dose inhaler therapy for asthma, bronchitis, and emphysema.

This review addresses the use of the metered dose inhaler (MDI) to administer aerosol therapy in the treatment of asthma, bronchitis, and emphysema. Studies have shown that physicians' prescribing patterns for use of the inhaler have been inconsistent with optimal therapy. Furthermore, the medical literature suggests that the metered dose inhaler should replace the jet nebulizer in hospital and outpatient settings as a more efficient and cost-effective treatment method. All classes of aerosol drugs are now available for administration by the MDI. Reports suggest that patients whose conditions do not respond to treatment administered by the MDI may improve following instruction in the proper method of using the inhaler or by increasing the recommended dosage of medication for those receiving beta-adrenergic, anticholinergic, and glucocorticoid drugs. A consensus now recommends that aerosol glucocorticoids be considered the primary method of therapy for asthma; however, the effectiveness of glucocorticoids in the treatment of bronchitis and emphysema has not been determined. Although available data do not prove that drugs used in the treatment of asthma increase mortality, further study is recommended in view of the potential toxicity of these drugs.

Administration, Inhalation↗
PubMed2004

The development of a novel high-dose pressurized aerosol dry-powder device (PADD) for the delivery of pumactant for inhalation therapy.

The performance of a novel dry powder inhaler designed to deliver exceptionally high doses was investigated using pumactant as a model powder. Pumactant (a synthetic lung surfactant consisting of a phospholipid mixture), with a 90th percentile particle size of 2.92 microm is highly cohesive, has a high moisture affinity (6.2% w/w at 45% RH), and is predominantly amorphous. The device (pressurized aerosol dry-powder delivery [PADD]) utilizes pressurized gas to aerosolize a powder bed from a reservoir and delivers it through a conventional mouthpiece. The influence of loaded dose on dry powder delivery and can pressure on aerosolization efficiency was investigated. Analysis of the delivered dose studies suggested a linear relationship between loaded dose and delivered dose (R(2) = 0.96, for loaded doses of 0-250 mg), with a delivery efficiency of 70%. Analysis of the aerosolization efficiency using a Marple Miller type impactor suggested fine particle fractions (particles with an aerodynamic diameter of <5 microm) of approximately 30% using canister pressures of 8-14 bars. These results indicate that the PADD device may be a useful tool in delivering high-dose medicaments, as a carrier-free formulation, to the deep lung.

Administration, Inhalation↗
PubMed1997

Investigation of urinary levels of salbutamol in asthmatic patients receiving inhaled therapy.

AIM: Some studies have indicated that over-reliance on inhaled bronchodilator (beta 2-agonist) therapy may worsen asthma control and increase morbidity. The aim of this study was to measure urinary concentrations of salbutamol, the most commonly used bronchodilator, in a relatively large sample of asthmatic patients and examine the potential value of the concentration as an indicator of over-use of salbutamol. METHOD: The urinary concentrations of the drug were measured in 'spot' urine samples from 102 asthmatic patients (64 community patients and 38 hospital inpatients). A solid-phase extraction technique, using a phenyl-bonded phase and a reversed-phase ion-pair high-performance liquid chromatography assay with UV-detection were developed and used to measure both unchanged salbutamol concentrations and total salbutamol concentrations after enzymatic hydrolysis of the metabolite. In addition, salbutamol concentrations were corrected for urine dilution, with the measured drug expressed per gram of urinary creatinine. RESULTS: The hospital patients were generally older, had greater disease severity, were more likely to be receiving prophylactic therapy and had received more salbutamol in the past 24 h. The urinary concentrations of salbutamol varied enormously between patients. The median concentrations of unchanged and total drug were 0.38 microgram/ml (range 0-34.4 micrograms/ml) and 2.55 micrograms/ml (range 0-49.8 micrograms/ml), respectively. Even when controlling for dosage in the preceding 24 h, there was a 262-fold and 810-fold variation in the urinary concentrations for unchanged and total salbutamol, respectively, among the community patients. Modest correlations were found between salbutamol concentrations and dosage administered in the preceding 24 h (Spearman's r = 0.67 and 0.54 for unchanged and total drug, respectively; P < 0.001). The correlations improved only slightly with correction for urine dilution (Spearman's r = 0.69 and 0.57 for unchanged and total drug, respectively; P < 0.001). CONCLUSION: This enormous inter-patient variability, which may be largely due to differences in the pharmacokinetics of salbutamol and inhaler technique, may play a role in the observed worsening of asthma control with the regular use of inhaled bronchodilator drugs and warrants further investigation. Measuring urinary concentrations of salbutamol in spot samples provides only a relatively crude indication of the extent of use of inhaled salbutamol in the preceding 24 h.

Administration, Inhalation↗