Comparative oral bioavailability of conventional propranolol tablets and a new controlled-absorption propranolol capsule

Abstract

The relative bioavailabilities of a new once-a-day propranolol formulation (Duranol) and conventional propranolol tablets (Inderal) were evaluated in six healthy male volunteers in a randomized balanced cross-over study. During the first treatment period, subjects were administered either a single 160 mg Duranol capsule at 9 a.m. or 80 mg Inderal at 9 a.m. and 9 p.m. Plasma propranolol concentrations were measured at 0, 2, 3, 4, 5, 6, 8, 10, 12, 13, 14, 15, 16, 24 and 36 hours after the 9 a.m. dose.

Mean peak plasma propranolol concentrations (Cmax) of 92.7 ng/ml at 2 hours and 53.9 ng/ml at 2.8 hours were recorded after administration of the first and second Inderal doses, respectively. After Duranol dosing, the Cmax of 85 ng/ml was not significantly different than the Inderal values; however, Duranol's tmax of 8 hours was significantly greater (p < 0.05) than either tmax recorded for Inderal. Compared to data obtained after administration of conventional propranolol tablets, mean propranolol concentrations were significantly lower at 2, 3 and 4 hours (p < 0.01) and significantly higher at 8, 10 and 12 hours (p < 0.05) after Duranol administration. The lengths of time plasma levels remained at 5, 10, 20, 30, 40, 50, 60, 70 and 80 ng/ml were not significantly different between the two products. In addition, the mean AUCs for Inderal and Duranol after 12 hours (380.2 vs 434.0 ng ml<⁻¹h, respectively), 24 hours (728.0 vs 728.8 ng ml⁻¹h, respectively), 36 hours (813.0 vs 826.8 ng ml⁻¹h, respectively), or from time 0 to infinity (838.6 vs 860.4 ng ml⁻¹h, respectively) were not significantly different.

These results indicate no loss in bioavailability despite a significantly prolonged absorption time for Duranol relative to conventional propranolol tablets. These results suggest that in the treatment of cardiovascular disorders an equivalent single dose of Duranol can be substituted for the daily requirements of conventional propranolol administered in divided doses.