Effect Site and Latency to Peak Effect
For many opioids, there is a significant time lag between peak
concentration in the plasma and peak drug effect. This time lag, or hysteresis,
is a function of drug movement into and action within the effect site, or biophase.
The time lag is particularly important when giving opioids by bolus administration
such as during PCA therapy.
Flow of drug to the effect compartment is a first-order process
and can be elucidated by estimating keo
, a first-order rate constant for
elimination of drug from the effect compartment. In general, the fentanyl congeners
(especially alfentanil and remifentanil) have a short keo
half-life (t1/2
keo
),
whereas morphine's blood-brain equilibration time is much longer. In humans, it
was reported that after intravenous administration of sufentanil (10 µg), fentanyl
(100 µg) and alfentanil (1 mg) peak brain concentrations were achieved at 45
sec, 5 minutes, and 6 minutes for alfentanil, sufentanil, and fentanyl, respectively
( Fig. 11-17
).[328]
This difference is due to the different times required to reach blood-brain equilibrium.
After single bolus administration, alfentanil and remifentanil exhibit rapid speed
of offset, because effect-site concentrations begin to fall immediately after achieving
a rapid peak.[329]
