β-受容体遮断薬の標準的狭心症治療量とβ_1及び血管拡張性受容体 : 結合占有率との関係の受容体結合占有理論に基づく解析

概要

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Beta-adrenoceptor blocking agents (β-blockers)have been widely used for the treatment of angina pectoris. The average/standard therapeutic doses vary widely among β-blockers with the maximum of about a 120-fold difference. In order to clarify the mechanism of this difference, we analyzed retrospectively the pharmacological effects of β-blockers in consideration of the β_1-receptor binding affinity and the vasodilative activity on the basis of pharmacokinetics and the receptor occupancy theory. The analysis was performed on eight β-blockers without a vasodilative effect and on four β-blockers with a vasodilative effect. The β_1-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 and on the dissociation constant of receptors. The estimated receptor occupancies were 87±6% or 88±10% for the β-blockers with or without a vasodilative effect, respectively, and a significant difference was not observed between these groups. These results suggest that the β_1-receptor occupancies may be a principal indicator for the therapeutic effects for angina pectoris regardless of their vasodilative effects.
公益社団法人日本薬学会の論文
1999-07-01