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

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Abstract
1 The metabolism of (+)‐, (‐)‐ and (±)‐salbutamol by sulphoconjugation was determinedin vitrousing human lung cytosol and bronchial epithelial BEAS‐2B cell homogenate.2 For the lungs the intrinsic clearance (Vmax/Km) value for the pharmacologically active (‐)‐salbutamol (0.49 ± 0.32 ml min‐‐1g‐1protein) exceeded that of (+)‐salbutamol (0.046 ± 0.028 ml min‐1g‐1protein) by 11‐fold. This was mainly due to a difference inKmvalue, which was 16 times higher for (+)‐salbutamol (1300 ± 170 μM) than for (‐)‐salbutamol (83 ± 12 μM).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.