Pharmacokinetic Model

Pharmacokinetic Model

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The pharmacokinetic model is loosely based on the work of Maitre and Shafer who described a method of predicting anaesthetic drug concentrations based on a three compartment model of drug distribution and elimination.

 

Their model has been subject to three additional refinements:

1.The ability to calculate drug concentrations at effector sites has been added.
2.The ability to define the potency of any drug at any effector site has been added.
3.A mechanism of competitive antagonism has been added.

 

The basic structure of the model is shown bellow.

 

PKPDModel

 

The output of the model is illustrated by the response of the patient to the administration of heparin (and its reversal by protamine) in the graph below.

 

HeparinReversal

 

Before the administration of 10,000 units of heparin, the Activated Clotting Time (ACT) is ~ 130 secs. After the administration of heparin, the ACT rises rapidly to about 325 seconds. 10 minutes later, the patient is given 100 mg of protamine and virtually complete reversal of the anticoagulant effect of the heparin occurs.

 

References:

Maitre PO, Shafer SL. A simple pocket calculator approach to predict anesthetic drug concentrations from pharmacokinetic data.  Anesthesiology. 1990 Aug;73(2):332-6.