Clinical pharmacokinetics and pharmacological actions of a long-acting formulation of propranolol

The pharmacokinetics and pharmacodynamics of a long-acting formulation of 60 mg propranolol (Inderal LA; in the following briefly called LA) once a day were compared with those of conventional propranolol (Inderal; in the following called CV) 20 mg three times a day, by a double-blind cross-over method in healthy volunteers. After a single oral dose with LA in 10 subjects, the blood level slowly increased to reach the peak plasma level (Cmax) of 11.56 +/- 2.15 ng/ml (mean +/- SE) at 5 h which was lower than that of CV (42.93 +/- 19.26 ng/ml). However, the peak plasma level was almost constant for another 5 h with LA (11.03 +/- 2.38 ng/ml at 10 h). The elimination half-life with LA was significantly longer than with CV (6.5 +/- 1.0, 3.9 +/- 0.5 h, respectively). The plasma level at 24 h did not differ between LA and CV (3.34 +/- 0.92, 5.47 +/- 1.38 ng/ml, respectively). LA and CV were orally administered for 8 consecutive days in 6 subjects. The plasma level after LA accumulated and Cmax was 1.6 times higher and the area under the time-concentration curve (AUC) 1.7 times higher than on Day 1, but no accumulation of the plasma level was seen after CV. On Day 8 the plasma level after 24 h of LA turned-out to be higher than that of CV (4.4 +/- 2.2, 3.5 +/- 1.5 ng/ml). Although the exercise heart rate was significantly more suppressed by CV than LA on Day 1, the difference disappeared on Day 8.(ABSTRACT TRUNCATED AT 250 WORDS)