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·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.

Patients with asthma are a target group for medication with β2-agonists, often in combination with corticosteroids. Salbutamol is commonly marketed as racemate. R-Salbutamol carries β2-agonistic property whereas S-salbutamol does not. The racemate undergoes stereoselective sulphatisation by sulfotransferases mainly in the gut and liver, so that S-salbutamol rests for a longer time in the body and reaches higher plasma levels than R-salbutamol. Ten patients with mild stable asthma and at present without cortisone medication were given racemic salbutamol as ventoline 4 mg orally. Plasma and urine levels were estimated until 24 hr after ingestion. For comparison healthy volunteers were treated in the same way.The group of asthma patients was then treated with budesonide inhalations 800 μg daily for one week and the initial programme resumed. Non-cortisone-treated asthmatic patients displayed higher levels of both R- and S-salbutamol in plasma than did healthy volunteers after one single ingestion of racemic salbutamol (CMAX both comparisons P<0.05). Plasma levels of salbutamol isomers in cortisone-treated asthmatic patients resembled the levels in volunteers. The most plausible explanation for the discrepancy in values between asthmatic patients and volunteers is a defective metabolic function by asthmatic patients possibly enzymatic in origin.

Racemic salbutamol, a β₂-adrenoceptor agonist used for dilatation of airways, has recently been shown to induce lessened relaxation of bronchial smooth muscle and partial loss of bronchoprotection, seen as increased hyperresponsiveness, after regular treatment. The racemate undergoes stereo-selective disposition, giving higher plasma levels of S-salbutamol than that of bronchodilating R-salbutamol, thus raising S : R ratios after repeated administration. Our aim was to evaluate whether increased bronchial hyperresponsiveness (BHR) could be found even after 1 day of repeated salbutamol inhalations, with β₂-receptor-induced bronchial smooth muscle relaxation remaining and whether this would be associated with plasma levels of either enantiomer. Fifteen patients with stable asthma, aged 19–54 years, were included in a randomized, cross-over study. An indirect bronchial challenge method was used [voluntary isocapnic hyperventilation of cold air (IHCA)], and airway condition tested by means of impulse oscillometry. Racemic salbutamol was inhaled three times during a 6-h period. IHCA was performed and plasma concentrations of enantiomers were measured 4 h after the last dose. Tests were also performed without preceding drug treatment. β₂-Agonist-produced bronchial dilatation and protection persisted in the majority of the 15 patients 4 h after repeated inhalations of salbutamol during 1 day. In only two of the 15 patients we could trace increased BHR after salbutamol. Neither dilatation nor protection could be linked to plasma levels of either R- or S-salbutamol. The underlying mechanisms of BHR remain unknown and are dissociated from β₂-receptor-mediated dilatation.

Twenty-six patients with mild to moderate asthma were enrolled in a doubleblind, randomised, cross-over study. Bronchial response to provocation, given as isocapnic hyperventilation with cold air (IHCA), was measured before and after one week's medication with single isomer R-salbutamol and racemic R/S-salbutamol, respectively. Doses of 0.63 mg R-salbutamol or 1.25 mg R/S-salbutamol were inhaled by nebuliser three times daily dming medication-weeks. Impulse oscillometry (IOS) as well as forced expiratory volume dming one second (FEV₁) were methods used to identify bronchial response to provocation. Two patients withdrew from the investigation due to side-effects, one from Rthe other from R,S-salbutamol.

The aim of this study was to investigate the effects from medication with R,S- and R-salbutamol on bronchial response to provocation.

Intra-individual differences of < 2% between days in baseline values, measured as total airway resistance (R5) by IOS and ≤ 1% measured as FEV₁. indicated comparable resting bronchial conditions. After a week's medication no significant differences in airway responsiveness to provocation could be demonstrated irrespective of the medication used.

Neither regular medication with inhaled corticosteroids up to 800 mg/day nor any increase in ahway inflammation, was found to influence the results.

Plasmaconcentrations of R-salbutamol were intra-individually lower after R- than after R,S-salbutamol. Considerable amounts of S-salbutamol were retrieved in plasma after medication with pure R-salbutamol.

We conclude that we were unable to demonstrate favourable effects of R-salbutamol over R,S-salbutamol regarding response to provocation with cold air after medication of one week's duration.