【摘要】 家兔静脉注射5mg/kg心得安。药一时曲线呈二室模型。观察了心得安血浆浓度与抑制静止心率,Q—T_C及山静脉注射25μg/kg异丙肾上腺素引起心动过速的相关性。血药浓度与抑制心率全过程的数学式为:E=20·C^6.32/(C^6.32+29.4^6.32)。抑制异丙肾上腺素引起心动过速的数学式为:E=100·C^2.01/(C^2.01+73.7^2.01)·式中29.4及73.7是相应的C₅₀（ng/ml）。用此数学式可从药效而预测所需血药浓度,或由血药浓度预测药效。大多数药代动力学参数的个体间差异大于8倍。产生50%最大药效的血药浓度C₅₀亦有变异,个体间差异3.6—5.2倍。心得安血浓度100ng/ml抑制心率的药效相差4.4倍。提示在TDM实践中应注意药效学的个体差异。更多还原

【Abstract】 The logC of propranolol in plasma vs time curve follow-ing iv bolus of 5 mg/kg showed two-compartment open model in rab-bits. The correlation between plasma levels and the inhibiting effectson the resting heart rate, Q-Tc and tachycardia evoked by iv 25μg/kgisoprenaline was noticed. A mathmatic equation describing the wholecourse of plasma levels in relation to suppressive effects on heart rate isas follows: E=20·C^6.32/(C^6.32+29. 4^6.32). The equation for inhibitingisoprenaline-induced tachycardia is expressed by E=100·C^2.01/(C^2.01+73. 7^2.01). The two constants 29.4 and 73. 7 in equations are C₅₀ （ng/ml）.Prediction of plasma level from pharmacological effects or inverselybecame possible by using these equations. The individual variation inmost of pharmacokinetic parameters is more than 8 folds. The C₅₀plasma concentration producing 50% of maximal pharmacological effects,is also varied, ranging from 3. 6-5. 2 folds. There was 4.4 folds in sup-pressive effect of 100 ng/ml on heart rate. It is suggested that empha-sis should be put on pharmacodynamic variation during TDM practice.更多还原