Pharmacology for Anaesthesia and Intensive Care

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Section IBasic principles

ln(C)

ln(A)

ln(B)

time

α

β

Figure 6.12.Bi-exponential decline.Foratwo-compartment model plasma concentration

declines with a rapid exponential phase that has time constantα,this is due largely to

distribution. Once distribution has occurred plasma concentration falls at a slower exponential

rate–terminal elimination – with a time constantβ.Neitherαnorβequate to any one

particular rate constant for the model.

compartment. This is clearly seen with remifentanil where k 12 is 0.4 and k 21 is 0.21;

these are relatively large rate constants and so there is relatively little contribu-

tion from distribution and the behaviour of remifentanil is much closer to a one-

compartment model than is that of fentanyl.

The volume of the central compartment is found by dividing the dose given, X, by

C 0 .Asinthe simple model, the central and peripheral compartments do not corre-

spond to actual anatomical or physiological tissues. Thus, the central compartment

is often larger than just the plasma volume, representing all tissues that, in pharma-

cokinetic terms, behave like plasma.

Three compartments

Modelling drug behaviour using three compartments requires three exponential

processes. The equation for the plasma concentration (C) is now given by:

C=A·e−αt+B·e−βt+G·e−γt.