Enantiomeric disposition of inhaled, intravenous and oral racemic-salbutamol in man - no evidence of enantioselective lung metabolism

Aims To establish whether enantioselective metabolism of racemic (rac)-salb utamol occurs in the lungs by determining its enantiomeric disposition foll owing inhalation, in the absence and presence of oral charcoal, compared wi th that following the oral and intravenous routes. Methods Fifteen healthy subjects (eight male) were randomized into an open design, crossover study. Plasma and urine salbutamol enantiomer concentrati ons were measured for 24 h following oral (2 mg) with or without oral charc oal (to block oral absorption), inhaled (MDI; 1200 mu g) with or without or al charcoal and intravenous (500 mu g) rac-salbutamol. Systemic exposure (p lasma AUC(0, infinity) and urinary excretion (Au-24h) of both enantiomers w ere calculated, and relative exposure to (R)-salbutamol both in plasma (AUC ((R)-)/AUC((S)-)) and urine (Au(R)-/Au(S)-) was derived for each route. Rel ative exposure after the inhaled with charcoal and oral routes were compare d with the intravenous route. Results AUC((R)-)/AUC((S)-) [geometric mean (95% CI)] was similar following the intravenous [0.32 (0.28, 0.36)] and inhaled with charcoal rates [0.29 (0.24, 0.36); P = 0.046], but was far lower following oral dosing [0.05 (0. 03, 0.07); P < 0.001]. Similar results were found when relative exposure wa s analysed using Au-24h. Conclusions These results show no evidence of significant enantioselective presystemic metabolism in the lungs, whilst confirming it in the gut and sy stemic circulation, indicating that the (R)- and (S)-enantiomers are presen t in similar quantities in the airways following inhaled vac-salbutamol.