Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs.

Article Details

Citation

Copy to clipboard

Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE

Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs.

J Pharmacol Exp Ther. 1997 Apr;281(1):226-32.

PubMed ID

9103501 [ View in PubMed

]

Abstract

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 microg/kg/min remifentanil, 500 microg/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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Remifentanil	Mu-type opioid receptor	Protein	Humans	Yes	Agonist	Details