The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients.

BACKGROUND It has been suggested that R-albuterol produces bronchodilation that is comparable with that of racemic albuterol (RS-albuterol) on a 4:1 dose-for-dose basis but systemic side effects on a 2:1 basis, implying better therapeutic ratio for R-albuterol. OBJECTIVE We sought to carefully compare the bronchodilating and systemic effects of R- and RS-albuterol by using a crossover study design. METHODS Twenty asthmatic patients (15.1%-28.7% FEV(1) reversibility) were given R-albuterol (6.25-1600 microg), S-albuterol (6.25-1600 microg), RS-albuterol (12.5-3200 microg), or placebo in a crossover, double-blind, placebo-controlled fashion. Cumulative doses were given with a Mefar dosimeter, and FEV(1), heart rate, and plasma K(+) levels were measured 20 minutes after each dose. RESULTS Both R- and RS-albuterol produced dose-related improvement in FEV(1) and, at higher doses, increased heart rate and decreased plasma K(+) levels. Neither placebo nor S-albuterol had any significant effect. Individual estimates of the potency ratio for R-albuterol/RS-albuterol were calculated and summarized across all subjects. The geometric mean potency ratio for effects on FEV(1) was 1.9 (95% CI, 1.3-2.8), on HR of 1.9 (95% CI, 1.3-2.9), and on K(+) level of 1.7 (95% CI, 1.3-2.1). CONCLUSION All pharmacologic effects of RS-albuterol reside with the R-enantiomer, and S-albuterol is clinically inactive. The R-albuterol/RS-albuterol potency ratios for local (FEV(1)) and systemic effects (heart rate and K(+)) are similar, suggesting a comparable therapeutic ratio for R-albuterol and RS-albuterol in asthmatic subjects.

[1]  J. Lötvall,et al.  Targeting Drugs to the Airways by Different Inhalation Devices , 1999, BioDrugs.

[2]  J. Dow,et al.  Enantiomeric disposition of inhaled, intravenous and oral racemic-salbutamol in man--no evidence of enantioselective lung metabolism. , 2001, British journal of clinical pharmacology.

[3]  D. Handley.  The asthma-like pharmacology and toxicology of (S)-isomers of β agonists☆☆☆ , 1999 .

[4]  B. Waldeck.  Enantiomers of bronchodilating beta2-adrenoceptor agonists: is there a cause for concern? , 1999, The Journal of allergy and clinical immunology.

[5]  S. Gawchik,et al.  The safety and efficacy of nebulized levalbuterol compared with racemic albuterol and placebo in the treatment of asthma in pediatric patients. , 1999, The Journal of allergy and clinical immunology.

[6]  A. Jones,et al.  Determination of the enantiomers of salbutamol and its 4-O-sulphate metabolites in biological matrices by chiral liquid chromatography tandem mass spectrometry. , 1998, Rapid communications in mass spectrometry : RCM.

[7]  H. Nelson,et al.  Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. , 1998, The Journal of allergy and clinical immunology.

[8]  B. Lipworth,et al.  Pharmacokinetics and extrapulmonary beta 2 adrenoceptor activity of nebulised racemic salbutamol and its R and S isomers in healthy volunteers. , 1997, Thorax.

[9]  B. Lipworth,et al.  Dose-Response of Inhaled Drugs in Asthma , 1997, Clinical pharmacokinetics.

[10]  J. Benovic,et al.  Comparison ofR-, S-, andRS-albuterol interaction with human β1 and β2-adrenergic receptors , 1996 .

[11]  X. Nie,et al.  Albuterol. A pharmaceutical chemistry review of R-, S-, and RS-albuterol. , 1996, Clinical reviews in allergy & immunology.

[12]  D. Boulton,et al.  Enantioselective disposition of salbutamol in man following oral and intravenous administration. , 1996, British journal of clinical pharmacology.

[13]  M. Perrin-Fayolle.  Salbutamol in the treatment of asthma , 1995, The Lancet.