No abstract

Many pharmaceutical companies sell salbutamol in metered-dose inhalers (MDI) for the treatment of asthma. However, the therapeutic equivalence of the more recently released generic products has not been compared with the original patented product in children. Twenty children with mild to moderate asthma, presently asymptomatic and with normal lung function, were randomly allocated to receive 200 microg of inhaled salbutamol (Albuterol) from three MDIs prepared by different manufacturers: the original Glaxo product and two generic products. The three drug formulations and placebo were given 10 min before a methacholine challenge test to determine the degree of protection provided against methacholine-induced bronchoconstriction (MIB) by each salbutamol aerosol. Tests were performed on 4 consecutive days. Doubling concentrations of methacholine were inhaled until the forced expired volume in 1 sec (FEV(1)) decreased by 20% from its baseline value. Compared to placebo, all patients increased significantly the provocation concentration that decreased FEV(1) by 20% (PC(20)) by more than one doubling concentration after inhaling each of the three salbutamol aerosols. The effectiveness was not significantly different between medications (P = 0.8). There was a small but significant difference among MDIs in aerosol particle size and total and fine-particle dose released per actuation. However, no relation was found between aerosol particle size or released dose and the protective effect. This study shows that the three tested brands of salbutamol MDI protected asthmatic children equally from MIB. When prescribing these salbutamol MDIs to prevent symptoms triggered by nonspecific stimuli in asthmatic children, the selection may be based on cost-benefit criteria.

Little is known about the ability of small-volume valved spacer devices to deliver a significant amount of an aerosolized drug to the lungs of babies. This study compared the in vitro delivery of salbutamol administered via Aerochamber-Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as the in vivo delivery using an animal model. The lung deposition study of technetium-99m-labeled salbutamol was conducted in six anesthetized, intubated (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was studied on three separate occasions, once with each spacer device. The amount of radioactivity deposited in the spacer device, the endotracheal tube, the lungs, or the body was measured by a gamma camera and expressed as a percentage of the emitted labeled dose. The emitted dose and particle size distribution of salbutamol via the three spacer devices were measured using unit dose sampling tubes and an eight-stage Anderson cascade impactor, respectively. The results were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the NES-spacer and Babyhaler were equivalent for delivering particles Ͻ5.8 m in diameter (NES-spacer ϭ Babyhaler Ͼ Aerochamber-Infant; p Ͻ 0.05). In vivo, the lung and body deposition was low with all spacer devices (range: 0.52-5.40% of the delivered dose) but greater with the NESspacer than with the Aerochamber-Infant or the Babyhaler (5.40 Ϯ 2.40%, 2.91 Ϯ 0.86%, 0.52 Ϯ 0.46%, respectively; p ϭ 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants. Small-volume spacer devices fitted with a face mask and inspiratory/expiratory valves have been developed for delivering pressurized metered-dose inhaler drugs to infants and newborns with various respiratory diseases (1-4). However, little is known about the ability of these spacer devices to deliver a significant amount of drug to the lungs of spontaneous breathing infants and a fortiori in intubated and mechanically ventilated infants and newborns.The radiotracer technique is the only method available for direct estimation of aerosol deposition in vivo. This technique is commonly used in adults, and has been used in several studies in infants (5-7). However, the exposure of small infants to radioisotopes remains a concern. Thus, performance is often projected from in vitro experiments (8 -10) or in vitro lung models (11,12), with data obtained at lower inspiratory flow rates and higher tidal volumes through the spacer devices than what would be encountered in clinical practice. Animal "infant" models (13, 14) may be suitable alternatives to assess pulmonary deposition of labeled drugs. Usually, rabbits are tracheotomized, mechanically ventilated, and killed, but this animal model poorly reflects the lung deposition of drug administered through spacer devices in spontaneously breathing children. Because oropharyngeal ...