From the opioid receptor to the whole animal: Pharmacokinetics and pharmacodynamics of fentanyl in the horse

In the first aim of this study, we compared the density and binding characteristics of opioid receptor subtypes in the horse, rat and guinea pig brain, using a radioligand binding technique to identify mu-, delta- and kappa-opioid receptors. While there were marked species differences in relative densities of opioid binding sites, all radioligands interacted with their binding sites with high, nanomolar affinity. In conclusion, the receptor density profile for the horse cerebral cortex and cerebellum was most similar to the rat cerebral cortex and guinea pig cerebellum, respectively.; Fentanyl is commonly used in human and small animal medicine as an adjunct to inhalant anesthesia. In order to evaluate the potential of fentanyl as an adjunct to anesthesia in horses, the pharmacokinetics of fentanyl must first be determined in anesthetized horses. Thus, the second aim was to describe the pharmacokinetics of fentanyl after IV administration of a single bolus of fentanyl to horses that were awake in treatment 1 and anesthetized with isoflurane in treatment 2. Anesthesia with isoflurane significantly decreased the volume of distribution at steady state and clearance of fentanyl and significantly area under the concentration-time curve extrapolated to infinity and the intercept of rapid distribution phase in comparison to awake horses. Thus, the pharmacokinetics of fentanyl were substantially altered in horses anesthetized with isoflurane.; Fentanyl decreases the minimum alveolar concentration (MAC) of inhaled anesthetics in humans and small animals. For our third aim, we hypothesized that intravenous fentanyl would dose-dependently decrease the MAC of isoflurane in horses. Following determination of baseline MAC of isoflurane, fentanyl was administered intravenously to target plasma concentrations of 1, 8, and 16 ng/ml. Isoflurane MAC was re-determined 45 min after fentanyl administration. Fentanyl concentrations of 0.72 and 8.43 ng/ml did not significantly alter the MAC of isoflurane, but an 18 (7)% isoflurane MAC reduction was observed at the 13.31 ng/ml concentration. In conclusion, these results encourage further study of fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesia in horses.