Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses

Reasons for performing study: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. Objectives: 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 μg/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 μg/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 and potential relevance: 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.