Bjornsson T D, Levy G
J Pharmacol Exp Ther. 1979 Aug;210(2):243-6.
The purpose of this investigation was to determine whether the time course of heparin activity (bioassayed heparin concentration) in plasma of rats during and after constant rate i.v. infusion of heparin can be predicted from the pharmacokinetic characteristics of a single i.v. bolus dose of heparin administered to the same animals. Five rats received a rapid i.v. injection of heparin, 320 to 517 U/kg, and on the following day, an i.v. infusion of heparin, 2.7 to 4.0 U/min/kg, for 10 to 11 hr. Heparin activity in plasma at the end of the infusion was about twice as high as predicted on the basis of the total clearance of the bolus dose. Even though the maximum heparin activity immediately after the bolus dose and at the end of the infusion were similar, the biologic half-life of heparin at the end of the infusion was about twice as long as that of the bolus dose. Apparently, the pharmacokinetics of heparin are time dependent. This may explain, at least in part, the clinical observation that heparin infusion rate must often be reduced after the initial days of therapy.
本研究的目的是确定在对同一组大鼠持续静脉输注肝素期间及之后，血浆中肝素活性（生物测定的肝素浓度）的时程是否可以根据给予这些动物的单次静脉推注剂量肝素的药代动力学特征来预测。五只大鼠接受了快速静脉注射肝素，剂量为320至517 U/kg，次日接受了静脉输注肝素，速率为2.7至4.0 U/（min·kg），持续10至11小时。输注结束时血浆中的肝素活性约为根据推注剂量的总清除率预测值的两倍。尽管推注剂量后即刻和输注结束时的最大肝素活性相似，但输注结束时肝素的生物半衰期约为推注剂量时的两倍。显然，肝素的药代动力学是时间依赖性的。这至少可以部分解释临床上的观察结果，即肝素输注速率在治疗初期后的几天内常常必须降低。
