Studies on the pharmacokinetics and pharmacodynamics of propranolol in hyperlipidemia

The lipophilic beta-adrenoreceptor antagonist propranolol has been studied to define its pharmacokinetic and pharmacodynamic characteristics in hyperlipidemic patients. A total of 48 subjects were allocated to four study groups: (1) healthy volunteers, (2) hypercholesterolemic patients, (3) hypertriglyceridemic subjects, and (4) patients with a mixed form of hyperlipidemia. Propranolol was given orally as a single dose of 80 mg. Heart rate was measured during 12 hours. At each point, the concentrations of propranolol were estimated. Moreover, heart rate and arterial systolic blood pressure were examined at rest and after a submaximal exercise test 3 hours after administration of propranolol (i.e., at the peak of propranolol concentration in the blood serum). A significant increase in the area under the serum concentration-time curve (AUC) by 39% and a reduction of the volume of distribution and total body clearance by 48% and 46%, respectively, without a significant change in the half-life time, were observed in patients with hypertriglyceridemia in comparison with the control group. The acceleration of exercise heart rate and the elevation of systolic blood pressure were comparable in all groups in the study, whereas blood serum concentrations of propranolol in patients with hypertriglyceridemia (group 3) and the mixed form of hyperlipidemia (group 4) were markedly altered from those observed in normolipemic subjects. No relationship between the concentration of propranolol and the heart rate in the group with hypertriglyceridemia was seen. In the light of this study, the authors suggest that lipid metabolism disturbances do not affect the pharmacodynamics of propranolol.