Systemic Availability of Oral Slow-Release Morphine in Man

In a within-patient crossover study on twelve patients we investigated plasma morphine concentrations for 48 hours after administration of intravenous morphine sulphate followed 24 hours later by oral MST Continus [MST]. Patients received either 10 mg i.v. morphine followed by 10 mg MST or 20 mg i.v. morphine followed by 2 X 10 mg MST tablets. Systemic clearance of morphine was low, being about 3 ml/min/kg after both intravenous and oral administration. The ratio of the areas under the concentration-time curve for MST relative to that for i.v. morphine was about 1:1 for 20 mg doses, but was significantly greater than 1:1 for 10 mg doses. The results suggest high oral systemic availability for morphine and low hepatic morphine metabolism.