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Publication - Dr Jo Murrell

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

    Citation

    Slingsby, LS, Murrell, JC, Taylor, PM & Sear, JW, 2016, ‘Effect of intramuscular methadone on pharmacokinetic data and thermal and mechanical nociceptive thresholds in the cat’. Journal of Feline Medicine and Surgery, vol 18., pp. 875-881

    Abstract

    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 liquidchromatography–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 (Tmax), time of onsetof 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 Tmax 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.

    Full details in the University publications repository