STEREOSELECTIVE SULFATE CONJUGATION OF SALBUTAMOL BY HUMAN LUNG AND BRONCHIAL EPITHELIAL-CELLS

1 The metabolism of (+)-, (-)- and (+/-)-salbutamol by sulphoconjugati on was determined in vitro using human lung cytosol and bronchial epit helial BEAS-2B cell homogenate. 2 For the lungs the intrinsic clearanc e (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 du e to a difference in K-m value, which was 16 times higher for (+)-salb utamol (1300+/-170 mu M) than for (-)-salbutamol (83 +/- 12 mu M). 3 T he stereoselectivity of sulphoconjugation of salbutamol was very simil ar in the BEAS-2B cells, although the absolute activity was considerab ly lower. 4 The enzyme catalyzing this reaction both in the lungs and in the BEAS-2B cells was the monoamine (M) form phenolsulphotransferas e. 5 These observations emphasize that the smooth muscle of the bronch i most likely are exposed to considerably higher concentrations of the potentially toxic (+)-enantiomer than of the bronchodilating (-)-enan tiomer during therapy with (+/-)-salbutamol.