Minimal residual disease prior to stem cell transplant for childhood acute lymphoblastic leukaemia.

OBJECTIVE

To evaluate the pharmacokinetics of four administration routes of oxycodone parenteral liquid (10 mg/mL), single intravenous and intramuscular injections and buccal and gastric administration, in children.

PATIENTS AND

PARTICIPANTS

Forty generally healthy children, aged 6-93 months, undergoing inpatient surgery.

METHODS

After induction of anaesthesia, children received a single dose of oxycodone 0.1 mg/kg intravenously (n = 9), intramuscularly (n = 10), buccally (n = 11) or via an orogastric tube into the stomach (n = 10). Regular blood samples were collected up to 12 hours, and plasma was analysed for oxycodone using gas chromatography-mass spectrometry (limit of quantification 1 microg/L).

RESULTS

The peak drug concentration observed was 57-110 (mean 82) microg/L after intravenous administration, 23-54 (34) microg/L after intramuscular administration, 3.9-14 (9.8) microg/L after buccal administration and 1.7-15 (9.2) microg/L after gastric administration. The time to peak concentration was 2-30 (16) minutes in the intramuscular group, 30-480 (221) minutes in the buccal group and 60-360 (193) minutes in the gastric group. The terminal elimination half-lives were closely similar in the four groups: 124-208 (163) minutes in the intravenous group, 162-227 (150) minutes in the intramuscular group, 73-234 (150) minutes in the buccal group and 80-246 (147) minutes in the gastric group. Area under the concentration-time curve (AUC) was 5037-8954 (6612) microg x min/L in the intravenous group, 3084-5524 (4473) microg x min/L in the intramuscular group, 1444-5560 (3658) microg x min/L in the buccal group and 692-3843 (2436) microg x min/L in the gastric group. The estimated bioavailability (AUC/mean intravenous AUC) of intramuscular oxycodone was 0.47-0.84 (0.68), that of buccal oxycodone 0.22-0.84 (0.55) and that of gastric oxycodone 0.10-0.58 (0.37).

CONCLUSION

The pharmacokinetics of intravenous oxycodone in children aged 6-93 months are fairly similar to those reported in adults. Intramuscular administration provides relatively constant drug absorption, but after buccal and gastric administration the interindividual variation in the rate and extent of absorption is large.