Pharmacokinetics of intramuscularly administered morphine in horses

Abstract

To determine the pharmacokinetics of morphine after IM administration in a clinical population of horses. Prospective clinical study. 77 horses. Morphine sulfate (0.1 mg/kg [0.045 mg/lb], IM) was administered to horses, and blood samples were obtained at predetermined time points. Plasma morphine concentrations were measured via liquid chromatography and mass spectrometry. In preliminary investigations, samples were obtained from 2 healthy horses at 12 time points (up to 12 hours after drug administration) and analyzed via 2-stage pharmacokinetic analysis. In the clinical phase, blood samples were obtained from 75 hospitalized horses at various times (total, 2 to 3 samples/horse) up to 9 hours after drug administration, and data were analyzed via a naïve pooled pharmacokinetic model. In the clinical phase, the apparent terminal half-life (t(½)) of morphine was approximately 1.5 hours, volume of distribution per bioavailability was approximately 4.5 L/kg, and clearance per bioavailability was approximately 35 mL/kg/min. Peak plasma concentration in naïve pooled analysis was 21.6 ng/mL and occurred approximately 4 minutes after administration. Morphine concentrations were below the limit of quantification ≤ 7 hours after administration in 74 horses. Adverse effects attributed to morphine administration were uncommon and considered mild. The short t(½) of morphine in horses suggested frequent administration may be needed to maintain targeted plasma concentrations. Variations in plasma concentrations suggested optimal dosages may differ among horses. The drug was well tolerated at the described dose, but patients receiving morphine should be monitored carefully.