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

The study explores how general anesthesia, particularly isoflurane, influences the behavior of the drug fentanyl and its primary metabolite, PMA, in horses. The research found that the rates of clearance of the fentanyl and PMA were significantly reduced in anaesthetised horses compared to awake horses.

Study Design and Methodology

• The study applied a balanced crossover design with two treatments and 4 horses in each group.
• In the first treatment, awake horses were given a single intravenous (i.v.) dose of fentanyl.
• In the second treatment, the horses were anaesthetised with isoflurane—a commonly used inhalant anaesthetic—and subsequently given the same single dose of fentanyl following a 30-minute equilibration period.
• The researchers measured the concentration levels of fentanyl and PMA in the horses’ plasma at different intervals. This was accomplished using liquid chromatography-mass spectrometry, a technique used for identifying and quantifying molecules in a mixture.

Key Findings

• The study found that isoflurane significantly decreased the clearance of fentanyl and PMA, which indicates that anesthesia slows the elimination process of these substances from the body.
• The volume of distribution, or the extent of a drug’s dispersion in the body, at steady state was also decreased for both fentanyl and PMA under anesthesia. This may influence the drug’s effect on the body and duration of its action.
• The elimination half-life of fentanyl, the time it takes for the body to reduce the drug’s concentration by half, was 1 hour in both awake and anaesthetized horses. Meanwhile, PMA’s elimination half-life was 2 hours in awake horses and 1.5 hours in anaesthetised ones.

Conclusion and Practical Application

• The study concluded that general anaesthesia with isoflurane notably alters the pharmacokinetics—the behaviour of a drug in the body—of fentanyl and PMA in horses.
• The pathways and rates of absorption, distribution, metabolism and excretion of these substances change in the presence of isoflurane.
• The findings provide valuable knowledge to determine appropriate loading and infusion doses for fentanyl, whether horses are awake or anesthetized. Thus, the information can be used to optimize pain management protocols in veterinary medicine, particularly in surgical procedures involving horses.