Therapeutic equivalence of three metered‐dose inhalers containing salbutamol (Albuterol) in protecting against methacholine‐induced bronchoconstriction in children with asthma

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.

Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo‐controlled, crossover study

“…Consequently, the US Food and Drug Administration advisory committees have recommended the use of methacholine challenge testing for assessing the pharmacodynamic properties of inhaled β 2 agonists [17]. A number of previous studies have used methacholine challenges to compare short‐acting inhaled β 2 agonists [18, 19]. Furthermore, a study using methacholine challenges to compare the long‐acting β 2 agonists formoterol and salmeterol was able to demonstrate a difference in dose–response that was not reflected in FEV 1 changes [12].…”

Dose–response relationship and reproducibility of urinary salbutamol excretion during the first 30 min after an inhalation

“…Any method used in bioequivalence studies should be reproducible and have a dose–response relationship. Although a dose–response relationship has been reported [2] a bronchoprovocation study comprising two doses from an innovator and generic product suggested that therapeutic equivalence may have been shown due to the plateau of the dose–response curve [3]. This assumption was made because the two products had a different emitted fine particle dose determined by in vitro methods.…”

A Study of Patient Responses to a Perceived Change in Salbutamol Metered Dose Inhalers

“…Although published clinical studies demonstrated that substituting brand name salbutamol with generic salbutamol resulted in an equivalent clinical response, [4][5][6] anecdotal reports of failure due to a lack of efficacy or adverse effects were not uncommon. In a carefully controlled clinical study, the therapeutic equivalence of three salbutamol MDIs was even demonstrated in a paediatric population, 7 but clinicians learning of 'failure' of a generic MDI product from their patients may be more likely to trust the report from their own patients than the results of a scientifically rigorous study conducted by unknown investigators. It is likely that any changes in 'objective measures', such as a decline in FEV 1 , would provide further 'concrete' evidence of the failure of the new generic product.…”