Morphine kinetics in cancer patients

Oral and intravenous morphine kinetics were studied in seven patients with cancer who needed continuous treatment with morphine because of severe chronic pain. Single oral (20 to 30 mg) and intravenous (4 mg) doses were given on separate days, followed by repetitive blood sampling for morphine analysis by gas chromatography. Volume of distribution ranged from 0.95 to 3.75 l/kg and serum clearance from 5.0 to 16.1 ml/min/kg. Oral morphine in doses that were more than five times the intravenous dose gave concentrations (at 10 and 120 min after dose) between 38 and 112 ng/ml. During the 0.25- to 8-hr period after the oral dose serum concentrations were higher than after the intravenous dose. There was a variation in oral bioavailability of 15% to 64% and an interindividual variation in terminal half-life from 58 to 465 min. These data warrant careful adjustment of the oral dose under close supervision of the patient at the onset of therapy.