Ritodrine sulphation in the human liver and duodenal mucosa: interindividual variability

The beta2-adrenoceptor agonist ritodrine has a bioavailability of 30% due to its presystemic metabolism and sulphation is an important metabolic route. The interindividual variability in the rate of ritodrine sulphation in 100 specimens of human liver and duodenum is reported. The final concentrations of ritodrine were 2 mM (duodenum) and 20 mM (liver). The mean estimates of ritodrine sulphation rate were 490 pmol x min(-1) x mg(-1) (duodenum) and 140 pmol x min(-1) x mg(-1) (liver). There was a 4-5-fold variation within +/- 2 SD units in the hepatic and duodenal rates of ritodrine sulphation. Statistical analysis revealed the presence of at least two subgroups of ritodrine sulphation. In the liver, 30% and 70% of the population fell into two subgroups with the mean estimates of ritodrine sulphation rate of 114 and 149 pmol x min(-1) x mg(-1), respectively (P < 0.05). In the duodenum, 25% and 75% of the population fell into two subgroups and the mean estimates of ritodrine sulphation rate were 332 and 538 pmol x min(-1) x mg(-1), respectively (P < 0.05). The rates of ritodrine and 4-nitrophenol sulphation correlated highly in the liver (r = 0.865; P < 0.001) and the rates of ritodrine and dopamine sulphation correlated highly (r = 0.914; P < 0.001) in the duodenum. In both tissues, the rates of ritodrine and (-)-salbutamol sulphation underwent a similar extent of variation and correlated highly. The intrinsic clearance of ritodrine sulphation was over one order of magnitude higher in the duodenum than in the liver suggesting that the duodenum is an important site of ritodrine sulphation.