Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs

The clinical effects and pharmacokinetics of medetomidine (MED) and its ena ntiomers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared i n a group of six beagle dogs. The dogs received intravenously (i.v.) a bolu s of MED (40 mu g/kg), DEX (20 and 10 mu g/kg), LEVO (20 and 10 mu g/kg), a nd saline placebo in a blinded, randomized block study in six separate sess ions. Sedation and analgesia were scored subjectively, and the dogs were mo nitored for heart rate, ECG lead II, direct blood pressure, respiratory rat e, arterial blood gases, and rectal body temperature. Blood samples for dru g analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of seda tion and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, t he analgesic effect of DEX20 lasted longer than the effect of the correspon ding dose of racemic medetomidine, suggesting greater potency for dexmedeto midine in dogs. Levomedetomidine had no effect on cardio-vascular parameter s and caused no apparent sedation or analgesia. The pharmacokinetics of dex medetomidine and racemic medetomidine were similar, but clearance of levome detomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.0 3 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).