EditorialsLevalbuterol and racemic albuterol: Are there therapeutic differences?☆,☆☆
Section snippets
Hypothesis: S-albuterol works in opposition to the bronchodilator and bronchoprotective effects of R-albuterol
If true in human beings, this adverse effect of S-albuterol would cause R-albuterol, administered as levalbuterol, to be significantly more potent than an equal amount of R-albuterol given in the racemic formulation. Let us first look in more detail at the studies whose conclusions supported this hypothesis. The study by Nelson et al evaluated the bronchodilator effects of the levalbuterol and racemic formulations in 362 adolescent and adult subjects treated with levalbuterol, racemic
Hypothesis: S-albuterol is responsible for development of tolerance to the beneficial effects of R,S-albuterol
If true in human beings, this would cause the tolerance after repeated administration of levalbuterol to be absent or at least smaller in magnitude than that associated with racemic albuterol. Only a study by Cockcroft et al21 addresses this hypothesis. They administered R-albuterol alone, S-albuterol alone, racemic albuterol (all enantiomers in equimolar doses), or placebo for 6 days. On days 0 and 7, they evaluated the protective effect of the R-albuterol on methacholine responsiveness. They
Hypothesis: S-albuterol increases airway hyperresponsiveness
If true, this would result in less hyperresponsiveness after administration of levalbuterol than after administration of the racemic formulation. The study by Nelson et al showed that after 4 weeks of treatment there was a small increase in baseline FEV1 with placebo or levalbuterol but not with racemic albuterol. This was statistically significant only in a subgroup of subjects using inhaled corticosteroids. The authors suggested that this might have been due to an increase in airway
Hypothesis: S-albuterol is responsible for inducing some or all of the paradoxical bronchospasm seen with racemic albuterol
If true, this would result in a lower incidence of paradoxical bronchospasm after treatment with R-albuterol than after treatment with R,S-albuterol. Unfortunately, there are no studies that directly test this hypothetical adverse effect of S-albuterol.
Hypothesis: S-albuterol itself causes some of the systemic effects seen with inhaled albuterol
No authors of published preclinical studies or of papers that reviewed these studies have actually posed this hypothesis. Nonetheless, 2 other groups of authors have addressed this issue in normal volunteers.22, 23 In addition, the current report by Lötvall et al4 addresses the issue in subjects with asthma. All of these reports concluded that all observed systemic effects of racemic albuterol are due to the R-enantiomer.
So where are we now regarding a basis for decision-making? Although the
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Reprint requests: Miles Weinberger, MD, Pediatric Department, University of Iowa Hospital, Iowa City, IA 52242.
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J Allergy Clin Immunol 2001;108:681-4.