Pharmacokinetics of Carfentanil and Naltrexone in Domestic Goats (Capra Hircus)

Abstract

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.

Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil and carfentanil

“…Carfentanil, the active ingredient of Wildnil, is a fentanyl analogue that is approved for veterinary use as a tranquilizing agent for sedation, as a hypnotic, and as anesthesia of animals such as elephants, gazelles, goats, horses, pigs, polar bears, rhinoceroses, seals, and wolves [ 23 – 29 ]. It has been extensively studied in animals since it was first synthesized [ 23 , 28 – 30 , 32 , 37 , 38 , 109 ], but a few human studies have been also reported [ 31 , 33 , 34 ].…”

“…Eight domestic goats were used for the clarification of the pharmacokinetic profile of carfentanil and naltrexone by Mutlow et al [ 29 ]. The animals were administrated with 40 μg/kg carfentanil intramuscularly, and after 30 min naltrexone (100 mg naltrexone/mg carfentanil) was administered for anesthesia reversal in several routes of administration (intravenous, intramuscular, and subcutaneous).…”

“…The pharmacokinetic profiling of plasma showed rapid carfentanil absorption and a rapid reversal of immobilization by naltrexone after all routes of administration. Carfentanil’s half-life (5.5 h) did not differ according to different administration routes [ 29 ].…”

“…Naloxone and naltrexone are opioid receptor antagonists and had been used in several cases for the reversal of the respiratory depression caused by carfentanil [ 29 , 109 , 129 ]. Naltrexone was evaluated for antagonizing carfentanil in mOR binding by Miller et al [ 109 ] in an animal study conducted in captive Rocky Mountain elk.…”

“…Carfentanil is the most potent of the commercially available fentanyl analogues [ 19 , 20 ]. It was synthesized in 1974 by a group of chemists at Janssen Pharmaceuticals, and since then it has been used in veterinary medicine as a tranquilizer for the sedation of large animals [ 21 – 29 ]. Carfentanil has been pharmacologically studied mostly in animals, but also in humans [ 23 , 28 – 39 ].…”