Pharmacokinetics of xamoterol glucuronidation in the rat in vivo and in liver perfusion.

Xamoterol has a phenolic hydroxyl group at which both sulphation and glucuronidation may occur. In the rat in vivo it is almost exclusively glucuronidated. In bile the glucuronide conjugate is the only metabolite of xamoterol. In urine equal amounts of the glucuronide conjugate and unchanged xamoterol are present, together with a small amount of the sulphate conjugate (approx. 1% of the dose). The t1/2 of excretion of the glucuronide in bile was the same as the t1/2 for excretion of unchanged xamoterol in urine. The t1/2 for urinary excretion of the glucuronide conjugate was longer than that for its biliary excretion. In the isolated perfused rat liver glucuronidation was also the almost exclusive metabolic pathway. The extraction ratio of xamoterol by the liver was approx. 0.15. Since xamoterol is a very water-soluble compound, and is almost exclusively glucuronidated in the rat, it is an excellent model substrate for investigations on the pharmacokinetics of glucuronidation in the rat in vivo and in isolated perfused organs.