Pharmacokinetics of oral morphine sulfate in dogs: a comparison of sustained release and conventional formulations.
The pharmacokinetics and bioavailability (F) of single dose sustained release morphine sulfate (OSRMS) and nonsustained release morphine sulfate (NSRMS) were compared to each other and to a bolus injection of morphine sulfate (MS) intravenously (i.v.) in dogs. Beagles (n = 6) were randomly assigned to 3 treatment groups: namely, OSRMS 15 mg orally, NSRMS 15 mg orally, and 15 mg i.v. Serum samples were drawn at intervals up to 480 min following oral and 420 min following i.v. administration. Serum was analysed for morphine concentration using a radioimmunoassay. Data were analysed using non-compartmental pharmacokinetics. The only statistically significant difference between OSRMS and NSRMS was maximum serum concentration (Cmax). There were trends toward longer time to maximum serum concentration (Tmax) and longer mean absorption time (MAT) for OSRMS when compared to NSRMS, but the differences were not statistically significant (P < 0.05). Pharmacokinetic parameters for both oral formulations exhibited large variability in the rate of absorption of MS from the gastrointestinal tract. Bioavailability of both OSRMS and NSRMS was low (15%-17%). As expected, the area under the concentration vs time curve (AUC) and Cmax for the i.v. data was significantly greater than for both oral groups, and Tmax and mean residence time (MRT) were significantly less following i.v. administration. There were no statistically significant differences among the 3 treatment groups for apparent volume of distribution at steady state (Vdss) or elimination parameters. The OSRMS formulation used in this study provided equivalent bioavailability to NSRMS in dogs, accompanied by large individual variability in drug absorption. It also did not appear that the sustained release formulation provided sufficiently prolonged release of morphine sulfate from the tablet matrix in dogs to allow prolonged dosing intervals compared to NSRMS.
Dohoo
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Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown.
Tasker
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D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004285:Dogs / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay / Q000379:methods / Q000662:veterinary; D013997:Time Factors
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009020:Morphine