The Effects and Terminal Phase Pharmacokinetics of a Transmucosal Fentanyl Formulation in Three Species of Great Apes
Oral administration of various anesthetics to primates has historically used pineapple juice, maple syrup, peanut butter, marshmallows, or honey.3,6 While these were good formulations for the species studied, these animals often remember they were drugged because the carrier was only given when the veterinarian was around. Recently, carfentanil was administered to chimpanzees (Pan troglodytes) transmucosally/orally by syringing a carfentanil solution onto the oral mucosa of the animals.3 This was deemed a successful method of anesthesia by the authors (5/5 chimps reached at least stage 4 of anesthesia).
Transmucosal fentanyl is approved for use in the United States as a preanesthetic agent in adults and children and for use by adults for breakthrough cancer pain. Using this formulation in primates that have been trained to accept and suck on placebo candy, fentanyl was absorbed transmucosally similarly to the pharmacokinetic profile in humans. When the fentanyl was chewed and swallowed, there was still a sedative effect. This study provides an alternative sedative regimen for nonhuman primate restraint and also yielded terminal phase pharmacokinetic data of transmucosal fentanyl in three species of great apes. Eight orangutans (Pongo pygmaeus), 10 chimpanzees, and four gorillas (Gorilla gorilla) housed at local zoological collections were used in this study. The animals have been trained to accept and slowly suck on a piece of placebo candy, given as a treat, following an overnight fast. On the day of the study, the animals were given a compressed powder formulation of fentanyl (Actiq®, Anesta Corporation, Salt Lake City, UT). The animals received transmucosal administration(s) of fentanyl at an intended dose of 15–20 µg/kg based on estimated body weight. Following fentanyl sedation, the animals were induced using an appropriate combination of Telazol® and medetomidine, Telazol®, or ketamine and midazolam administered via projectile dart. The pharmacokinetic/pharmacodynamic data obtained in these primate species were compared to the published data in rhesus monkeys (Macaca mulatta)7 and humans.1,2,4,5
This project was supported by a grant from the Morris Animal Foundation. The authors would also like to thank Drs. Adrian Mutlow, Nancy Boedecker, and Connie Ketz for their assistance with sample collection and animal training.
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