(-)-Salbutamol sulphation in the human liver and duodenal mucosa : interindividual variability

Abstract

1. Salbutamol is a β₂-adrenergic agonist used in the treatment of lung obstructive disease and premature labour. It has a bioavailability of 50 % and sulphation is the main route of its metabolism. (-)-Salbutamol retains most of the β₂-adrenergic activity and, thereby, we describe the interindividual variability in the sulphation rate of (-)-salbutamol in 100 specimens of human liver and duodenal mucosa. 2. The mean rate (pmol/min/mg) of salbutamol sulphation was 498 in the duodenum and 141 in the liver with 4-fold variation within ±2 SD units in both tissues. 3. A modelling approach based on the comparison of the best fittings obtained using a gaussian and the sum of two gaussian curves revealed the presence of two subgroups in the hepatic rate of salbutamol sulphation and their means were 69.5 and 105 pmol/min/mg (p < 0.05). In the duodenum, the rate of salbutamol sulphation approached normality. 4. The rates of salbutamol and 4-nitrophenol sulphation correlated highly (r = 0.853; p < 0.001) in the liver whereas in duodenum the rates of salbutamol and dopamine correlated highly (r = 0.914; p < 0.001). 4-Nitrophenol and dopamine are the diagnostic substrates of phenol- and catechol-sulphotransferases respectively. These findings are consistent with the view that the rate of salbutamol sulphation is higher in the gut than in liver and it varies considerably in both tissues.