· Intro
· Two compartments: features
· Two compartments: sources of error
· Alternative models
Aim of pharmacokinetic model: to predict drug concentration during induction, maintenance and offset of anaesthesia
Diagramme 

Graph and equation 
· Biexponential decay curve: C = Ae^{at} + Be^{bt} 
Description 
· Propofol injected into V_{1} · Effect correlates with [propofol] in V_{1} · Fast distribution phase (distribution+++ metabolism ++) · Slower terminal elimination phase (metabolism++ offset by redistribution+) 
Derivation 
· Experiment in healthy volunteers · Propofol infusion at various rate, various duration (1min to 8h) · Serial blood sampling · Plot Cp vs time · Nonlinear regression analysis > equations, rate constants, compartment volumes 
Suitability of propofol 
· Reasonably modelled by two compartments (V_{DC} 0.30.6L/kg, V_{DSS} 4L/kg) · Rapid distribution (t_{1/2}_{α} fast 2 mins, t_{1/2}_{α} slow 50 mins) · Slow terminal elimination (t_{1/2}_{β} 512 hours) 
Inaccurate modelling 
· Body has billions of discrete cell compartments, not 1 or 2 or 3 · Variation in compartment volumes (e.g. shock), clearance rate (e.g. organ failure) · Inaccurate for induction kinetics (cardiac output and central blood volume more important) · Small sample size of experiments 
Inaccurate assumptions 
· No delay between reaching threshold Cp and onset of effect (e.g. lag described by k_{e0}) · [Drug] in V_{1} correlates immediately with effect (e.g. effect site may be in periphery e.g. rocuronium) · Elimination always from V_{1} (e.g. remifentanil metabolized in periphery) · Elimination not always first order (e.g. thiopentone zero order in physiological range) 
Consequences of error 
· Overdose > CVS toxicity · Underdose > awareness 
Single compartment 
· Not a good representation · Wholebody equilibration not immediate · Predicted loading dose based on V_{DSS} is fatal 
Three compartment 
· Better model for most drugs · E.g. propofol: t_{1/2}_{α} fast, t_{1/2}_{α} slow and t_{1/2}_{β} 
Four or more compartments 
· No significant advantage over three 
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