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  • Title: Tolerance to the bronchoprotective effect of beta2-agonists: comparison of the enantiomers of salbutamol with racemic salbutamol and placebo.
    Author: Cockcroft DW, Davis BE, Swystun VA, Marciniuk DD.
    Journal: J Allergy Clin Immunol; 1999 Jun; 103(6):1049-53. PubMed ID: 10359885.
    Abstract:
    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.
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