Pharmacokinetics of heparin. II. Studies of time dependence in rats.

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.