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Section IBasic principlesContext-sensitive half-times0501001502002503003500123456789101112
duration of infusion, hoursCSHT, minpropofol
alfentanil
fentanyl
remifentanilFigure 6.14.Variation in contex-sensitive half-time (CSHT) with duration of infusion.
This demonstrates the difference between propofol and fentanyl due to the more rapid
distribution and re-distribution kinetics of fentanyl and the more rapid elimination of propofol.
For short infusion times, fentanyl has a shorter CSHT than alfentanil, but after 2.5 hours,
alfentanil has a relatively constant CSHT compared with that for fentanyl, which continues to
increase.models. For remifentanil, where this ratio is less than 1, the opposite is true; there is
very little variation in CSHT. Context-sensitive half-time is a more useful indicator of
adrug’s behaviour in a given clinical setting. The variation of context-sensitive half-
time with duration of infusion for different intravenous agents is shown in Figure
6.14.Itmust be remembered that after one CSHT, the next period of time required
for plasma concentration to halve again will not be the same as the CSHT and is
likely to be much longer. This reflects the increasing importance of the slower re-
distribution and metabolism phases that predominate after re-distribution has taken
place. This explains the emphasis on half-timerather than half-life: half-lives are
constant whereas half-times are not.Non-linear kinetics
Sofar we have considered models in which first-order kinetics determines elimi-
nation of drug from the body. Metabolic processes are usually first-order, as there
is a relative excess of enzyme over substrate, so enzyme activity is not rate limit-
ing. However, in certain situations, some metabolic enzymes become saturated and
obey zero-order kinetics, in which the rate of change of plasma drug concentration is