美托洛尔血药浓度与抑制心率效应关系

Relation between plasma level of metoprolol and its inhibiting effect on heart rate

家兔６只，１０ｍｇ／ｋｇ美托洛尔肌注，药物体内代谢呈二室模型，高血压患者５例，一次口服美托洛尔片剂５０ｍｇ，药物体内代谢呈一室模型。家兔和高血压患者，血药浓度（Ｃｐ）与抑制心率效应（Ｅ）的关系均为Ｅ＝Ｅｍａｘ·Ｃｐ~ｓ／［Ｃｐ~ｓ＋Ｃｐ（５０）~ｓ」。Ｃｐ（５０）为引起半数最大效应的血药浓度，家兔Ｃｐ（５０）个体间相差１７．４５倍，高血压患者Ｃｐ（５０）相差６．０９倍，提示药物浓度监测应注意药效学的个体差异。

The relation between the plasma level of metoprolol and the inhibiting effect on the heart rate was studied in conscious rabbits and the essential hypertensive patients.The plasmaconcentration-time profile showed a two-compartment model after 10 mg/kg im to rabbits and a one-compartment model after oral administration to patients.The correlation between the plasma levels and the inhibiting effect on the heart rate was expressed by the E=Emax·Cps/[Cps+Cp (50)s].Prediction of plasma level from pharmacological effects or vice versa became possible by using this equation,The Cp(50) varied l7.45 folds in rabbits and 6. 90folds in patients.It is suggested that emphasis should be put on pharmacodynamic variation during TDM practice.