Pharmacokinetics of parenteral and oral sustained-release morphine sulphate in dogs

The pharmacokinetics of single-dose morphine sulphate (MS) administered intravenously (i.v.) and intramuscularly (i.m.) and of oral sustained-release morphine sulphate (OSRMS) were studied in dogs. Beagles (n = 6) were randomly assigned to six treatment groups using a Latin square design. Treatments included MS 0.5 and 0.8 mg/kg i.v. and i.m. and OSRMS 15 and 30 mg orally (p.o). Serum samples were drawn at intervals up to 420 min following parenteral MS and 720 min following OSRMS. Serum was analysed for morphine concentration using a radioimmunoassay. Pharmacokinetic analysis of the results revealed that MS was eliminated by a first-order process best described by a two-compartment model. For i.v. and i.m. data there were no statistically significant differences (P < 0.05) between steady-state volume of distribution, half-life of elimination and plasma clearance. As expected, area under the concentration vs. time curve (AUC) was significantly greater for the 0.8 mg/kg dosage for i.v. and i.m. routes, and time to maximum serum concentration was significantly longer following i.m. administration. For OSRMS there were no significant differences between dosage for any parameter (AUC, Cmax, tmax, t1/2, F) and prolonged absorption of the drug occurred over approximately 6 h. Bioavailability (F) for both oral dosages was approximately 20%. The i.m. route is an effective method for rapid and complete delivery of MS to dogs. OSRMS may be useful in the provision of long-term analgesic therapy in dogs, but further work is required to verify the safety and effectiveness of this preparation.