Pharmacokinetics and Pharmacodynamics of Three Alternative Routes of Naltrexone for the Reversal of Carfentanil Immobilization in Domestic Goats (Capra capra)
Carfentanil is a potent synthetic opioid commonly used to immobilize non-domestic ungulates with immobilization reversed by the opioid antagonist naltrexone. The currently recommended method of administration of naltrexone is to give 100 mg naltrexone for each mg of carfentanil administered, and to give one quarter of the calculated dose intravenously (i.v.) and three quarters of the calculated dose subcutaneously (s.c.).1 However, there are no published reports on the pharmacokinetics of either parenterally administered carfentanil or naltrexone in ungulates. Renarcotization is a significant problem but the cause is not fully understood.2,3 The purpose of this study was to correlate the pharmacokinetics and pharmacodynamics of intramuscularly (i.m.) administered carfentanil and naltrexone administered by i.v., i.m., or s.c. injection. The data from this study will be used as a model to assist with determining the most appropriate use of naltrexone in non-domestic ungulates and to help indicate the possible mechanism of renarcotization.
Eight adult domestic goats (Capra capra) were randomly assigned to one of three groups. Each was immobilized on three occasions with 40 µg/kg carfentanil administered i.m. Each immobilization was reversed 30 min after carfentanil administration with 4 mg/kg naltrexone administered either i.m., i.v., or s.c. Each animal was immobilized with all three protocols using a randomized block design. Blood samples were collected at 5, 10, 15, 20, 30, 40, 50 min and 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hr after carfentanil administration. The quantitation of carfentanil, naltrexone and possible metabolites in plasma was done using a validated liquid chromatography/mass spectroscopy (LC/MS) method.
All goats became recumbent and unresponsive within 84±18 sec (mean±SD) but the depth of anesthesia varied between individuals from sedation with occasional struggling to light anesthesia. All immobilizations were rapidly and completely reversed, independent of naltrexone route. The pharmacodynamics of each route were very similar: time to standing was 147±62 sec for i.m. naltrexone, 138±59 sec for i.v. naltrexone and 205±60 sec for s.c. naltrexone. There does not appear to be any advantage in dividing the naltrexone dose into i.v. and s.c. portions, and the smoothest recoveries were associated with i.m. injection. The pharmacodynamic data suggests that i.m. administration of naltrexone at 100 times the dose of carfentanil is appropriate in the domestic goat to reverse carfentanil. A mild renarcotization consisting of slight depression and somnolence was noted in most of the goats at 1.5–4 hr after reversal.
We are very grateful to Pamela Foran, Marie Goatley, and Hisako Mutlow for their help with sample collection. This study was funded with a grant from the Dean’s Fund, College of Veterinary Medicine, Kansas State University.
1. Trexonil product label information. Wildlife Pharmaceutics, Inc. Ft. Collins, Colorado.
2. Allen JL. 1989. Renarcotization following carfentanil immobilization of nondomestic ungulates. J. Zoo Wildl. Med. 20(4): 423–426.
3. Haigh JC. 1990. Opioids in zoological medicine. J. Zoo Wildl. Med. 21(4): 391–413.