Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations.

摘要

The kinetics and dynamics (inhibition of exercise tachycardia) of two controlled-release preparations of propranolol (Elanolol and Inderal LA) were examined in six normal volunteers. Conventional propranolol (Inderal) was also studied for comparison purposes. As compared to conventional propranolol (120 mg), single doses of Elanol (120 mg) and Inderal LA (160 mg) produced a smoother serum level profile, with lower and delayed peak times. Dose-corrected AUC0-24 values were greater after Elanol than after Inderal LA (651 +/- 147 vs 402 +/- 159 ng ml-1 h, means +/- s.e. mean, P greater than 0.05). The profile of inhibition of exercise tachycardia mirrored closely that of the serum levels. At steady state, all regimens studied (Inderal 40 mg three times daily; Elanol 120 mg once daily; Inderal LA 160 mg once daily) ensured relatively sustained serum levels and a stable degree of pharmacological effect. Dose-corrected AUC0-24 values were 797 +/- 148 ng ml-1 h after Inderal, 908 +/- 113 ng ml-1 h after Elanol and 602 +/- 122 ng ml-1 after Inderal LA. The bioavailability of Inderal LA was significantly lower than that of the other preparations. These results demonstrate that long-acting formulations of propranolol can be developed which are not necessarily associated with reduced bioavailability secondary to enhanced first-pass metabolism.