Tolerance to the bronchoprotective effect of beta2-agonists: comparison of the enantiomers of salbutamol with racemic salbutamol and placebo

J Allergy Clin Immunol. 1999 Jun;103(6):1049-53. doi: 10.1016/s0091-6749(99)70178-8.


Background: Regular use of racemic salbutamol results in the partial loss of its bronchoprotective effect. The 2 enantiomers of salbutamol, the bronchodilator R-salbutamol and nonbronchodilator S-salbutamol, are now available.

Objective: We sought to compare the effect of regular use of S-salbutamol, R-salbutamol, racemic salbutamol, and placebo on the bronchoprotective effect of a single dose of racemic salbutamol against methacholine-induced bronchoconstriction.

Methods: Eleven of 13 well-controlled beta2 -agonist-free asthmatic subjects completed a double-blind, randomized study comparing racemic salbutamol 2.5 mg, S-salbutamol 1. 25 mg, R-salbutamol 1.25 mg, and diluent placebo nebulized and inhaled 3 times daily for 6 days (>/=6-day washout period). Ten to 12 hours after the last dose, the subjects performed measurement of FEV1, methacholine PC20, and a repeat methacholine PC20 done 1 hour after the first methacholine test and 10 minutes after 2 puffs (200 microgram) of racemic salbutamol administered from a metered-dose inhaler. The primary endpoint was the methacholine PC20 dose shift (Deltalog PC20/log 2) from before to after administration of 200 microgram of racemic salbutamol.

Results: The methacholine dose shift was 3.2 doubling doses (9-fold increase in methacholine PC20 after 200 microgram of racemic salbutamol) during the placebo treatment and was unaltered (3.2) after administration of S-salbutamol. The dose shift was significantly lower after both the R-salbutamol and racemic salbutamol treatments (2.2 and 2.6 doubling doses, respectively); there was no significant difference between R-salbutamol and racemic salbutamol. There was no treatment effect on baseline FEV1, baseline methacholine PC20, or bronchodilation.

Conclusion: Regular treatment with racemic salbutamol or R-salbutamol, but not S-salbutamol, results in a partial loss of bronchoprotection, without loss of bronchodilation, compared with placebo.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Adult
  • Albuterol / pharmacology
  • Bronchi / drug effects*
  • Bronchial Provocation Tests
  • Bronchoconstriction / drug effects
  • Bronchodilator Agents / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Tolerance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Stereoisomerism


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Placebos
  • Albuterol