A model of the first pass passage of drugs from i.v. injection site to the heart based on the work of Upton RN, 1996. Models the kinetics and dynamics of induction of anaesthesia (lignocaine) in sheep.

Description

 (abstract excerpt) A general model based on indicator dilution principles of the initial 
 distribution and effects of drugs in a target organ after i.v. bolus administration is 
 presented. The model was validated from previous studies of myocardial pharmacokinetics 
 and pharmacodynamics of lignocaine in sheep. It is proposed that i.v. drug injection 
 produces a concentration “peak” of drug in venous blood, which is attenuated by 
 vascular mixing, and lung and heart kinetics, as the drug is transported from the 
 injection site to the heart where it exerts its effects. The model predicted that 
 the first passage of this peak through the heart was the principal component of 
 myocardial concentrations of lignocaine for 10 min after injection before recirculation 
 became important. 

 Injection rate, cardiac output and myocardial blood flow are important determinants 
 of the magnitude of the first pass peak. This model provides a physiological framework 
 for analyzing the initial distribution of drugs and gives the user a feel for the importance 
 of dosage, injection duration and blood flow in targeting an organ specific dosage level.
 It is considered a 'comp2' model as the organ (heart) is modeled as a simple two compartment 
 blood-tissue exchange (CTEX). 	

Equations

The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.