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

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Abstract

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.

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