Pharmacokinetics and pharmacodynamics of intranasal and intramuscular administration of naloxone in working dogs administered fentanyl.

Abstract

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field. OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs. ANIMALS: Ten healthy, working dogs aged 1.7&#x2009;&#xb1;&#x2009;1&#x2009;year and weighing 26&#x2009;&#xb1;&#x2009;3&#x2009;kg. METHODS: In this randomized, controlled cross-over study dogs received either 4&#x2009;mg of naloxone IN or IM 10&#x2009;minutes after fentanyl (0.3&#x2009;mg IV) administration. Sedation was assessed at baseline and 5&#x2009;minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120&#x2009;minutes after reversal with naloxone. Blood samples for naloxone detection were obtained at 0, 5, 10, 30, 60 and 120&#x2009;minutes. Pharmacokinetic parameters and sedation scores were compared between IM and IN naloxone groups. RESULTS: There was a significant increase in sedation score from baseline (0.25 [-4 to 1] IM; 0 [-2 to 1] IN) after fentanyl administration (11 [5-12] IM; 9.25 [4-11] IN), followed by a significant reduction at 5 (0.5 [-0.5 to 1.5] IM; 1.25 [-1.5 to 4.5] IN) through 120&#x2009;minutes (-0.5 [-2 to 1] IM; 0 [-4.5 to 1] IN) after reversal with naloxone. Route of administration had no significant effect on sedation score. Maximum plasma concentration was significantly lower after IN administration (11.7 [2.8-18.8] ng/mL IN, 36.7 [22.1-56.4] ng/mL IM, P&#x2009;<&#x2009;.001) but time to reach maximum plasma concentration was not significantly different from IM administration. CONCLUSION AND CLINICAL IMPORTANCE: Although IM administration resulted in higher naloxone plasma concentrations compared to IN, reversal of sedation was achieved via both routes after administration of therapeutic doses of fentanyl.