Steady-state pharmacokinetics of oral sustained-release morphine sulphate in dogs

The pharmacokinetics of steady-state oral sustained-release morphine sulphate (OSRMS) were studied in dogs. Beagles (n = 6) were randomly assigned to one of two treatment groups. Treatments included 15 mg OSRMS every 8 h for 4 days, or 15 mg OSRMS every 12 h for 4 days. Serum samples, drawn at intervals for the final 24 h of drug administration were analysed for morphine concentration using radioimmunoassay. Pharmacokinetic analysis revealed that there were no significant differences between trough serum concentrations for the concentration-time curves within either treatment group, indicating that steady-state pharmacokinetics had been achieved. There were no significant differences in time to maximum serum concentration among the three sections of the concentration-time curve for the 8-h group or between the two sections of the curve for the 12-h group. Area under the concentration-time curve and maximum serum concentrations were significantly greater for the section of the curve following dosing at 7:30 h than following dosing at 19:30 h in the 12-h treatment group. This chronopharmacokinetic variability was not present in the 8-h treatment group. OSRMS provides sustained periods of elevated serum concentrations following administration every 8 or 12 h at a clinically applicable dosage. The clinical implications of the chronopharmacokinetic variability seen with 12-hourly administration are not known. This formulation has potential for the treatment of chronic pain in dogs, but further studies of efficacy and safety following long-term administration are required.