Pharmacokinetics and pharmacodynamics of meperidine after intramuscular and subcutaneous administration in horses

Objective: To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Study design: prospective, randomized, blinded, crossover trial. Animals: Six adult horses weighing 494 ± 33 kg. Methods: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were collected at various time points for 24 hours. Accelerometry data were obtained for 8 hours to measure locomotor activity. Data were analyzed with a mixed effects model, and α was set at.05. Results: Meperidine terminal half-life (T_1/2), maximal plasma concentrations, and time to maximal concentration were 186 ± 59 and 164 ± 56 minutes, 265.7 ± 47.2 and 243.1 ± 80.1 ng/mL at 17 ± 6, and 24 ± 13 minutes for IM at subcutaneous administration, respectively. No effect of treatment or time was observed on thermal or mechanical thresholds, heart rate, respiratory rate, locomotor activity, frequency of defecations, or fecal weight (P >.2 for all). Conclusion: Maximum meperidine concentrations were achieved quickly with a short T_1/2 in both treatment groups. Neither IM nor subcutaneous meperidine influenced thermal or mechanical threshold or physiological variables. Clinical significance: The short half-life and lack of detectable antinociceptive effect do not support IM or subcutaneous administration meperidine at 1 mg/kg for analgesia in horses.