Pharmacokinetics of glucuronidation of propranolol following oral administration in humans.

Pharmacokinetic and bioavailability parameters of propranolol were estimated in 10 healthy adult subjects after single oral doses of two commercial tablet formulations of propranolol hydrochloride (2 X 40 mg). Plasma concentrations of propranolol were determined by a high-performance liquid-chromatographic (HPLC) assay. Peak plasma concentrations of propranolol glucuronide were 6-8 times those of the corresponding peak propranolol plasma concentrations. The mean resident time (MRT) of propranolol and of propranolol glucuronide was determined for each subject for both formulations. The MRT of the parent drug was found to be longer than the MRT of the glucuronide metabolite for each of the subjects examined. Statistical moment analysis indicated that this phenomenon is attributable to extensive presystemic glucuronidation of the parent drug.