Marked variation in oxycodone pharmacokinetics in infants

Abstract

The pharmacokinetics of oxycodone (13-hydroxy-7,8-dihydrocodeinone) has been studied in adults and in children who are older than 6 months but there is no information on the disposition of oxycodone in neonates and young infants. The aim of this study was to study the pharmacokinetics of oxycodone in infants varying in age from 0 to 6 months. Twenty-two infants undergoing surgery were given postoperatively an intravenous bolus of 0.1 mg.kg(-1) of oxycodone hydrochloride. Ten of the patients were younger than 1 week (group 1), six from 1 week to 2 months (group 2) and six from 2 to 6 months (group 3). Plasma samples were collected for the analysis of oxycodone concentrations up to 24 h. Pharmacokinetics were characterized by noncompartmental methods. The median (range) values for the clearance (Cl) were 9.9 (2.3-17.2), 20.1 (3.7-40.4) and 15.4 (14.8-80.2) ml.min(-1).kg(-1) in the above three groups. The values for volume of distribution at steady-state were 3.3 (1.9-4.7), 5.6 (1.3-8.5) and 3.2 (1.8-6.0) l.kg(-1) and for elimination half-life (t(1/2)) 4.4 (2.4-14.1), 3.6 (1.6-11.6) and 2.0 (0.8-3.9) h, respectively. Both Cl (r = 0.46) and half-life (r = -0.46) were correlated to the age of the patient (P < 0.05). There were 13 patients who were on mechanical ventilation at the time of oxycodone administration. None of the spontaneously breathing infants had hypoventilation which required assistance during the study. The values for Cl and t(1/2) varied greatly between the subjects. This variability was most pronounced in the two youngest groups. Routine dosing of oxycodone in young infants may be dangerous. The dose of oxycodone must be titrated individually.