Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats

Abstract

Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.

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

“…Unexpectedly, the results reported in the present study showed a low absorption of both DEX and MET following co-administration TA B L E 3 Median and range of pharmacokinetic parameters calculated with noncompartmental analysis after oral transmucosal (OTM) or intramuscular (IM) simultaneous administration of dexmedetomidine (10 μg/kg) and methadone (0.4 mg/kg) in 12 dogs drug volume that is proportional to the amount of drug administered (Porters et al, 2014).…”

“…Such a high administration volume could likely have hindered absorption. In fact, according to the results from another study, a high volume of drug administered using the OTM route leads to partial losses during administration and to the swallowing of a drug volume that is proportional to the amount of drug administered (Porters et al, ).…”

“…However, in these studies, the drugs that were assessed were not administered in combination with other molecules and were therefore not influenced by the possible physical–chemical interferences of the formulation or pharmacological effects. Only one study (Porters et al, ) reported the pharmacokinetic profile of DEX combined with buprenorphine in cats following OTM or IM routes of administration. Porters et al () determined similar results suggesting lower drug absorption by OTM compared to the IM route of administration and reported high variability in pharmacokinetic parameters, such as C max , T max and AUC.…”

“…Only one study (Porters et al, ) reported the pharmacokinetic profile of DEX combined with buprenorphine in cats following OTM or IM routes of administration. Porters et al () determined similar results suggesting lower drug absorption by OTM compared to the IM route of administration and reported high variability in pharmacokinetic parameters, such as C max , T max and AUC. These results were explained with the same hypotheses, (high administration volume, ptyalism and peripheral vasoconstriction).…”

“…Additionally, the first-pass metabolic effects on orally administered drugs are avoided with an OTM administration, and the rich blood supply to the oral mucosa allows drugs administered in this way to reach systemic therapeutic concentrations (Messenger, Hopfensperger, Knych, & Papich, 2016;Sattar, Sayed, & Lane, 2014;. In cats, this option was extensively evaluated in several trials (Bortolami, Slingsby, & Love, 2012;Ferreira, Rezende, Mama, Hudachek, & Aguiar, 2011;Ko et al, 2011;Santos et al, 2010;Wells, Glerum, & Papich, 2008) and was successfully used in a study comparing IM and OTM administration of DEX and buprenorphine (Porters et al, 2014). In dogs, some studies have been published on the clinical aspects or pharmacokinetics of OTM administration, and some of the evaluated sedatives were α-2 agonists (Cohen & Bennett, 2015;Messenger et al, 2016) and benzodiazepines (Aldawsari, Lau, Babu, Arnold, & Platt, 2018;Zhang, Niu, Zhang, & Streisand, 2002) or opioids (Abbo et al, 2008;Ko et al, 2011;Streisand et al, 1995).…”