McAllister R G
Clin Pharmacol Ther. 1976 Nov;20(5):517-23. doi: 10.1002/cpt1976205517.
A model for the intravenous administration of propranolol by a bolus-infusion technique designed to rapidly produce, then maintain, predicted plasma drug concentrations was derived from elimination kinetics in single-dose studies. Prospective testing of this model in 6 adult male subjects revealed a close correlation between predicted and observed drug levels; desired plasma concentrations were achieved within 5 min and maintained over the 30-min study period. By subtracting previously given bolus doses from the dose calculated as needed to produce a desired plasma level, progressive increases in predicted propranolol levels could be effected, with apparent maintenance of equilibrium. Correlations between the bolus doses and infusion rates and the plasma drug levels were consistent and significant, and constitute nomograms from which the dose of drug required to produce a desired plasma level may be approximated. The clearance of propranolol declined slightly as the drug plasma level increased, but did not significantly affect the accuracy of the model.
通过推注-输注技术静脉注射普萘洛尔的模型是从单剂量研究的消除动力学推导而来，该技术旨在快速产生并维持预测的血浆药物浓度。在6名成年男性受试者中对该模型进行前瞻性测试，结果显示预测药物水平与观察到的药物水平密切相关；在5分钟内达到所需血浆浓度，并在30分钟的研究期内维持。通过从为产生所需血浆水平而计算出的剂量中减去先前给予的推注剂量，可以实现预测的普萘洛尔水平逐渐升高，且明显维持平衡。推注剂量和输注速率与血浆药物水平之间的相关性一致且显著，构成了列线图，据此可以估算出产生所需血浆水平所需的药物剂量。随着药物血浆水平升高，普萘洛尔的清除率略有下降，但并未显著影响模型的准确性。
