Pharmacokinetics of dexmedetomidine,MK-467 and their combination following intramuscular administration in male cats

Objective

To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats.

Study design

Prospective randomized crossover experimental study.

Animals

A total of eight healthy adult male castrated cats aged 1–2 years.

Methods

Cats were administered dexmedetomidine (25 μg kg^–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg^–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg^–1) IM with 300, 600 or 1200 μg kg^–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data.

Results

A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL^–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL^–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM.

Conclusions and clinical relevance

MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.