Variation in morphine pharmacokinetics in children with cancer

Abstract

Morphine plasma concentrations were determined in 19 children with cancer. A single dose of morphine, 0.09-0.15 mg/kg, was given intravenously over 3-5 min. The plasma concentrations of morphine ranged from 23 to 472 ng/ml at 10 min and from 6.1 to 20.8 ng/ml at 60 min after morphine administration. The morphine plasma concentration exceeded the reported average analgesic concentration of about 20 ng/ml in only 1 patient at 60 min and subsequently declined further except for 4 patients in whom plasma levels exhibited a secondary peak. The pharmacokinetics of morphine was studied in 6 children. The total clearance of morphine ranged from 9.03 to 53.4 ml/min/kg. The apparent volume of the central compartment and the apparent volume of distribution at steady state ranged from 0.17 to 1.10 and from 2.06 to 7.86 l/kg, respectively. The elimination half-life ranged from 0.86 to 7.55 h. These data indicate that an interindividual variation in morphine pharmacokinetics is one factor responsible for varying dosage requirements in children with cancer.