Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses.
BACKGROUND
In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined.


OBJECTIVE
To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2.


METHODS
A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry.


RESULTS
Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively.


CONCLUSIONS
Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.
Thomasy
S M
SM
K.L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California, Davis 95616, USA.
Mama
K R
KR
Whitley
K
K
Steffey
E P
EP
Stanley
S D
SD
D000768:Anesthesia, General / Q000379:methods / Q000662:veterinary*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005283:Fentanyl / Q000378:metabolism / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry / Q000662:veterinary; D006736:Horses / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D007262:Infusions, Intravenous / Q000662:veterinary; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D011650:Pulmonary Alveoli / Q000737:chemistry*
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007530:Isoflurane; D005283:Fentanyl