Effect of intramuscular methadone on pharmacokinetic data and thermal and mechanical nociceptive thresholds in the...

Objectives The aim of the study was to assess simultaneous pharmacokinetics and thermal and mechanical antinociception after intramuscular methadone (0.6 mg/kg) in 10 cats. Methods Thermal and mechanical threshold (TT and MT, respectively) testing and blood collection were conducted at baseline and up to 24 h after administration. Methadone plasma concentrations were determined by liquid chromatography-tandem mass spectrometry and pharmacokinetic parameters were estimated by a non-compartmental method. TT and MT were analysed using ANOVA ( P <0.05). Time of maximum plasma concentration (T_max), time of onset of antinociception and time of reaching cut-out threshold (TT 55°C; MT 30 Newtons [N]) were determined. Results TT and MT increased above baseline from 20-240 mins and 5-40 mins, respectively, after intramuscular (IM) administration ( P <0.005). Mean maximum delta T (measured as TT minus baseline threshold) was 7.9°C (95% confidence interval [CI] 4.3-11.6) at 60 mins and mean maximum delta F (measured as MT minus baseline threshold) was 4.2 (95% CI 1.6-6.7) N at 45 mins. IM methadone concentration-time data decreased curvilinearly, and gave a clearance estimate of mean 9.1 ml/kg/min (range 5.2-15.7) with median T_max at 20 mins (range 5-360 mins). Conclusions and relevance IM data followed classical disposition and elimination in all cats. Plasma concentrations after IM administration were associated with an antinociceptive effect, including negative hysteresis. These data can be used for devising dosing schedules for methadone in clinical feline practice.