Stereoselective sulphate conjugation of salbutamol by human lung and bronchial epithelial cells

1 The metabolism of (+)-, (-)- and (+/-)-salbutamol by sulphoconjugation was determined in vitro using human lung cytosol and bronchial epithelial BEAS-2B cell homogenate. 2 For the lungs the intrinsic clearance (V-max/K-m) value for the pharmacologically active (-)-salbutamol (0.49+/-0.32 ml min(-1) g(-1) protein) exceeded that of (+)-salbutamol (0.046+/-0.028 ml min(-1) g(-1) protein) by 11-fold. This was mainly due to a difference in K-m value, which was 16 times higher for (+)-salbutamol (1300+/-170 mu M) than for (-)-salbutamol (83 +/- 12 mu M). 3 The stereoselectivity of sulphoconjugation of salbutamol was very similar in the BEAS-2B cells, although the absolute activity was considerably lower. 4 The enzyme catalyzing this reaction both in the lungs and in the BEAS-2B cells was the monoamine (M) form phenolsulphotransferase. 5 These observations emphasize that the smooth muscle of the bronchi most likely are exposed to considerably higher concentrations of the potentially toxic (+)-enantiomer than of the bronchodilating (-)-enantiomer during therapy with (+/-)-salbutamol.