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Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers

B Schmekel, I Rydberg, B Norlander, KN Sjosward, J Ahlner, RG Andersson
European Respiratory Journal 1999 13: 1230-1235; DOI:
B Schmekel
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I Rydberg
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B Norlander
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KN Sjosward
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J Ahlner
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RG Andersson
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Abstract

Racemic R,S-salbutamol is taken to relieve bronchial constriction. Only the R-enantiomer has bronchodilating properties. The S-enantiomer has been proposed to cause in vitro bronchial hyperreactivity in guinea-pigs. Stereoselective elimination of salbutamol has been shown, with S-salbutamol being eliminated at a slower rate than R-salbutamol. This study questioned whether rates of stereoselective elimination were similar after oral or lung delivery, and whether the S:R ratio would increase after repeated inhalations in a situation resembling a common clinical use. Eighteen healthy volunteers received single-dose racemic salbutamol as a solution instilled in the trachea during anaesthesia, as inhaled micronized powder and/or as ingested tablets. Five volunteers inhaled repeated doses of racemic salbutamol. Concentrations in plasma and urine were measured using a technique which allowed chiral separation of samples with concentrations as low as 0.1 ng x mL(-1). The bioavailability of S-salbutamol was significantly higher than that of R-salbutamol after the different modes of administration. Stereoselective elimination was more pronounced after oral administration than after inhalation. Repeated inhalations resulted in successive increases in the S:R ratio as steady state was approached. In conclusion, the clinical consequences of increasing plasma concentrations of S-salbutamol need to be further assessed.

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Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers
B Schmekel, I Rydberg, B Norlander, KN Sjosward, J Ahlner, RG Andersson
European Respiratory Journal Jun 1999, 13 (6) 1230-1235;

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Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers
B Schmekel, I Rydberg, B Norlander, KN Sjosward, J Ahlner, RG Andersson
European Respiratory Journal Jun 1999, 13 (6) 1230-1235;
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