Pharmacokinetic modeling of heparin and its clinical implications.

Experimental work on heparin has indicated that its half-life increases with dose. Two models to describe heparin's pharmacokinetic behavior are proposed, and the parameters in the models are fitted to experimental data. Both models exhibit an apparent first-order decay with a "half-life" that increases with dose. It is shown that, even though both models exhibit a bolus half-life of from 1 to 2 hr, over 2 days can be required for true steady-state conditions to be achieved in these models when a constant intravenous infusion of drug is given. The clinical implications of these models are discussed. Suggestions are made for further research on heparin kinetics.