Plasma concentration-response relationships of two formulations of propranolol.

Abstract

The time-course of beta blockade induced by two formulations of propranolol was compared to their plasma concentration-time curves. Graded infusions of isoproterenol were used to assess the degree of beta blockade at different times after oral administration of 80 mg of propranolol to 11 healthy volunteers. The time-course of drug effect was measured as the decline of the systolic pressor dose 20 (SPD 20) and the chronotropic dose 20 (CD 20). Variability of plasma propranolol concentration was small, varying within subjects from 27% to 36% and between subjects from 19% to 28% at the various sampling times. Pharmacodynamic effects showed a similar reproducibility: intra-individual variation was 15% to 28% for CD 20 and 17% to 32% for SPD 20; interindividual variation was 10% to 24% for CD 20 and 13% to 23% for SPD 20. Pooling of the data of all subjects indicated a parallel decline of drug concentration and effect. However, three of the 11 subjects showed drug effects declining at a faster rate than drug levels. This dissociation between serum concentrations and effects points out the clinical relevance of complementing kinetic studies of propranolol with pharmacodynamic studies. The good reproducibility within subjects and the small interindividual variation suggests that isoproterenol dose-response curves may be a useful tool for such studies.