Clinical pharmacokinetics of a dexmedetomidine–methadone combination in dogs undergoing routine anaesthesia after buccal or intramuscular administration

Abstract

This study aimed to define the pharmacokinetic profiles of dexmedetomidine and methadone administered simultaneously in dogs by either an oral transmucosal route or intramuscular route and to determine the bioavailability of the oral transmucosal administration relative to the intramuscular one of both drugs, so as the applicability of this administration route in dogs. Twelve client‐owned dogs, scheduled for diagnostic procedures, were treated with a combination of dexmedetomidine hydrochloride (10 μg/kg) and methadone hydrochloride (0.4 mg/kg) through an oral transmucosal route or intramuscularly. Oral transmucosal administration caused ptyalism in most subjects, and intramuscular administration caused transient peripheral vasoconstriction. The results showed reduced and delayed absorption of both dexmedetomidine and methadone when administered through an oral transmucosal route, with median (range) Cmax values of 0.82 (0.42–1.49) ng/ml and 13.22 (2.80–52.30) ng/ml, respectively. The relative bioavailability was low: 16.34% (dexmedetomidine) and 15.5% (methadone). Intramuscular administration resulted in a more efficient absorption profile, with AUC and Cmax values for both drugs approximately 10 times higher. Dexmedetomidine and methadone administered simultaneously by an oral transmucosal route using injectable formulations were not well absorbed through the oral mucosa. Nevertheless, additional studies on these drugs combination using alternative administration routes are recommended.

Pharmacokinetics of morphine in combination with dexmedetomidine and maropitant following intramuscular injection in dogs anaesthetized with halothane

“…Also, a high inter‐animal variation in the plasma concentration of dexmedetomidine observed in the present study might be resulting from dexmedetomidine administration after the induction of anaesthesia. Di Cesare et al () has also reported higher variability in plasma drug concentration of dexmedetomidine during the anaesthetic period which supports our explanation. The pharmacokinetics of i.m.…”

“…injection site compared to the published studies could also have contributed to the lower concentration of morphine. This study showed lower C max and similar T 1/2 of dexmedetomidine compared to a study by Di Cesare et al () who investigated the pharmacokinetic profile of 10 μg/kg dexmedetomidine administered i.m. in combination with methadone in dogs under anaesthesia (Di Cesare et al, ).…”

“…This study showed lower C max and similar T 1/2 of dexmedetomidine compared to a study by Di Cesare et al () who investigated the pharmacokinetic profile of 10 μg/kg dexmedetomidine administered i.m. in combination with methadone in dogs under anaesthesia (Di Cesare et al, ). The lower C max of dexmedetomidine in the present study was potentially due to the lower dose of the drug used.…”

Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis

“…OTM route allows one to avoid the first-pass metabolic effect and gastrointestinal degradation observed for the orally administered drugs. The rich blood supply of the oral mucosa allows drugs administered by this route to reach systemic therapeutic concentrations [22,23]. Moreover, OTM route represents an attractive alternative to other drug delivery routes, being a non-invasive, pain-free technique, which requires minimal restraint and does not cause distress in patients [46].…”

“…Oral transmucosal (OTM) route is gaining importance in veterinary medicine, because of the advantages it offers over oral, intramuscular and intravenous administration for systemic drug delivery [19][20][21]. These major advantages are its easy practicability, lack of pain during administration, high blood mucosal supply and avoidance of the hepatic first-pass effect or gastrointestinal degradation [22,23].…”