Publications

Fentanyl is approved for transmucosal use in the United States as a preanesthetic agent in human pediatric patients and in adults for breakthrough cancer pain. Using this formulation in three species of great ape, including eight orangutans (Pongo pygmaeus), nine chimpanzees (Pan troglodytes), and two gorillas (Gorilla gorilla), fentanyl was offered transmucosally at an intended dose of 10-15 microg/kg based on estimated body weight. The animals were trained to accept and suck slowly on a piece of placebo candy, given as a treat, after an overnight fast. On the day of the study, the animals were given the lollipop formulation of fentanyl. The resulting plasma concentrations of fentanyl supported transmucosal absorption, similar to that reported in humans. This study provides an alternative sedative regimen and yielded half-life data of transmucosal fentanyl in great apes. Although transmucosal fentanyl was a useful adjunct for sedating orangutans and gorillas, its acceptance by chimpanzees before chemical immobilization was suboptimal and unpredictable.

Using a crossover study design, the pharmacokinetics of carfentanil and naltrexone after i.v., i.m., and s.c. administration were determined in eight domestic goats (Capra hircus). Serial blood samples were taken up to 120 hr after carfentanil administration, and the plasma drug concentrations were determined using liquid chromatography and mass spectroscopy. All goats were immobilized with 40 microg/kg carfentanil i.m., although the resulting neurologic effects varied considerably. Plasma profiles showed rapid carfentanil absorption and a simple biphasic decline for 12-48 hr. Naltrexone given at 100 mg naltrexone/mg carfentanil 30 min after carfentanil administration produced rapid reversal of immobilization after all routes of administration. Variable fluctuations in the naltrexone plasma concentrations during the first 2.5-3.5 hr were observed, followed by a more consistent biphasic decline. The time to standing was significantly shorter after i.v. compared with s.c. naltrexone, although the time difference (1 min) had little clinical relevance. No statistically significant differences between the naltrexone pharmacokinetic parameters measured for the three routes of naltrexone administration were identified, although the recoveries after i.m. administration were, subjectively, the smoothest. The carfentanil half-life did not differ significantly in the goats given naltrexone by different routes. Although it is currently recommended that the naltrexone dose be divided into s.c. and i.v. portions, this practice does not appear to offer any benefit.