Remifentanil is a synthetic opioid in the phenylpiperidine series.1 It is a full agonist of M-opioid receptors.2 In dogs and humans, remifentanil does not undergo hepatic metabolism, but it is degraded by nonspecific plasma and tissue esterases, a unique feature among opioids.1,2 Remifentanil is therefore predicted to have a high clearance, independent of organ function. This was confirmed in humans because severe renal or liver disease does not influence the pharmacokinetics of remifentanil.3,4 An opioid with such characteristics would be useful in anesthesia of cats, for patients with liver or renal disease, as well as for balanced anesthesia, particularly for long procedures. Effects of drugs with a high clearance are expected to be less prolonged after long infusions than those of drugs with a lower clearance.5
Cats have been reported to be deficient in some pathways used in the metabolism of xenobiotics.6 This may lead to prolonged duration of action, increased adverse effects, or increased risk of toxicosis related to some drugs. Therefore, drugs not relying on hepatic biotransformation for their elimination are of particular interest in cats. Cats have also been reported to have lower cholinesterase and pseudocholinesterase activities than humans.7–9 Compared with dogs, results of 3 studies7–9 suggest that cats have similar or slightly lower cholinesterase and pseudocholinesterase activities. However, similar data for other types of plasma or tissue esterases have not been published. It is nevertheless possible that the clearance of remifentanil is different in cats than in dogs or humans.
Various factors have been reported to influence the concentration of cholinesterase and pseudocholinesterase in cat plasma and CSF.10 In that study, central depressants decreased CSF cholinesterase activity. Moreover, inhalant anesthetics influence the disposition of other drugs in cats, likely by decreasing blood flow to excretory organs.11 Inhalant anesthesia could therefore affect the disposition of remifentanil both directly, by affecting esterase activity, and indirectly, by decreasing blood flow to tissues able to metabolize this drug. It is nevertheless expected that the disposition of remifentanil in cats would be less affected by anesthesia than the disposition of drugs requiring organ metabolism.
The purpose of the study reported here was to characterize the disposition of remifentanil in conscious cats and in cats anesthetized with isoflurane. We hypothesized that remifentanil would be rapidly cleared from blood and that anesthesia with isoflurane would have minimal effect on its pharmacokinetics.
Liquid chromatographymass spectrometry
Area under the concentration-time curve
Area under the blood concentration-time curve extrapolated to infinity
Maximum blood concentration
Central venous catheterization set, Arrow International, Reading, Pa.
Insyte, Beckton-Dickinson, Sandy, Utah.
Rascal II, Ohmeda, Salt Lake City, Utah.
Medical Gas Analyzer LB2, Beckman, Anaheim, Calif.
Primary Standard, Matheson Gas Products, Cucamonga, Calif.
Acetic acid, Fisher Scientific, Pittsburgh, Pa.
Acetonitrile, Burdick and Jackson, Muskegon, Mich.
Water, Burdick and Jackson, Muskegon, Mich.
Formic acid, Aldrich, St Louis, Mo.
Fentanyl, Cerilliant, Round Rock, Tex.
Remifentanil, Abbott Laboratories, Abbott Park, Ill.
LTQ linear ion trap mass spectrometer, ThermoFisher Scientific, San Jose, Calif.
1100 Series, Agilent Technologies, Palo Alto, Calif.
Discovery HS C18, Supelco Inc, Bellefonte, Pa.
LCQuan, ThermoFisher Scientific, San Jose, Calif.
WinNonLin Pro, version 5.2, Pharsight, Cary, NC.
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