Kinetic analysis of therapeutic doses of beta-blockers for angina pectorisbased on receptor occupancy theory - Relationship between beta(1)-receptoroccupancy or vasodilative action and dose

Beta-adrenoceptor blocking agents (P-blockers) have been widely used for th e treatment of angina pectoris. The average/standard therapeutic doses vary widely among beta-blockers with the maximum of about a 120-fold difference . In order to clarify the mechanism of this difference, we analyzed retrosp ectively the pharmacological effects of beta-blockers in consideration of t he BI-receptor binding affinity and the vasodilative activity on the basis of pharmacokinetics and the receptor occupancy theory. The analysis was per formed on eight a-blockers without a vasodilative effect and on four P-bloc kers with a vasodilative effect. The Pi-receptor occupancies at the steady- state condition after oral administration of standard doses were calculated by the use of the data on the concentration of unbound agents in plasma an d on the dissociation constant of receptors. The estimated receptor occupan cies were 87+/-6% or 88+/-10% for the P-blockers with or without a vasodila tive effect, respectively, and a significant difference was not observed be tween these groups. These results suggest that the Pi-receptor occupancies may be a principal indicator for the therapeutic effects for angina pectori s regardless of their vasodilative effects.