Stereoselective pharmacokinetics of S-salbutamol after administration of the racemate in healthy volunteers.
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.
Schmekel
B
B
Dept. of Clinical Physiology, University Hospital, Linköping, Sweden.
Rydberg
I
I
Norlander
B
B
Sjöswärd
K N
KN
Ahlner
J
J
Andersson
R G
RG
D000280:Administration, Inhalation; D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism; D014132:Trachea
D000318:Adrenergic beta-Agonists; D000420:Albuterol