Animal model for pharmacokinetic approach to individualized heparin dosage regimen for i.v. infusion by constant rate to achieve and maintain a desired clotting time

Abstract

A pharmacokinetic approach was developed for the determination of an individualized heparin dosage regimen for an i.v. constant infusion rate. The rabbit was chosen as the animal model. From a test dose given i.v. the individual rate constant for loss of anticoagulant response was determined by measuring the whole blood activated clotting time. After selection of a desired clotting time to be maintained, the loading dose and infusion rate or heparin concentration at set infusion rate were calculated. In the three infusion studies used to illustrate this method, less than a 4% average deviation resulted between the actual clotting times and the desired clotting times.