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Vol. 281, Issue 1, 226-232, 1997
Departments of
Pharmacology and Clinical Pharmacology, Glaxo
Wellcome Inc., Research Triangle Park, North Carolina (J.F.H., M.K.J.,
K.T.M.), and
Department of Anesthesiology, University of Illinois at
Chicago, Chicago, Illinois (F.C., W.E.H.)
Remifentanil is an esterase-metabolized opioid developed for use in
anesthesia. The principal metabolite of remifentanil, GR90291, is
considered to be less potent. This study determined the relative
potency of GR90291 and alfentanil, compared with remifentanil, in
anesthetized dogs. Male dogs received thiamylal sodium, and anesthesia
was maintained using isoflurane and N2O in oxygen. Each dog
received a 5-min infusion of 0.5 µg/kg/min remifentanil, 500 µg/kg/min GR90291 and 1.6 mg/kg/min alfentanil in random order,
separated by 1 week. Serial blood samples were collected during and
after the infusion. The electroencephalogram was evaluated using
aperiodic analysis. The pharmacokinetics and pharmacodynamics of
remifentanil, GR90291 and alfentanil were determined using nonlinear
least-squares regression analysis. Remifentanil was rapidly eliminated,
with a terminal half-life of 6 min, compared with 19 min for GR90291
and alfentanil. Using the estimated concentration that elicits 50% of
the maximum response (EC50) for delta EEG activity and
spectral edge95, remifentanil was 4213 to 4637 times more
potent than GR90291 and 7.7 to 8.5 times more potent than alfentanil.
The blood-brain equilibration half-life was 2.3 to 5.2 min for
remifentanil, 0.39 to 0.41 min for GR90291 and 3.1 to 3.7 min for
alfentanil.
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