Presystemic and systemic glucuronidation of propranolol

The relative importance of presystemic and systemic glucuronidation of propranolol was examined in normal subjects given single oral and intravenous doses of propranolol. The areas under the plasma concentration--time curves (AUCs) of propranolol glucuronide (PG), 41 +/- 15 ng . hr/ml, and propranolol, 48 +/- 15 ng . hr/ml, were of the same order after the intravenous dose (0.05 mg/kg). After oral doses of 20 and 80 mg, the AUCs of PG were 302 +/- 105 and 1,398 +/- 409 ng . hr/ml; these were 7 times the AUCs of propranolol, 44 +/- 15 and 220 +/- 38 ng . hr/ml. The time lapse to peak concentration, 1.5 to 3.0 hr, and the plasma half-life, 3.2 to 3.7 hr, were the same for PG and propranolol. These results demonstrate glucuronidation as an important determinant of propranolol bioavailability.