Should the dosage of controlled-release oxycodone in advanced cancer be modified on the basis of patient characteristics?
OBJECTIVE
This study aimed to investigate whether the characteristics of patients with advanced cancer explain the variability in oxycodone clearance, with the potential for this information to determine maintenance dosing.


METHODS
Patients (n = 36) with advanced cancer who were receiving delayed-release oxycodone (Oxycontin®) (mean dose, 31.4 mg; range, 5-120 mg) mostly twice daily (mean duration = 80 days; range, 5-651 days) provided venous blood samples (n = 139, median = 3 per patient) drawn from 0.25 to 23.4 h post-dose. Plasma was assayed for oxycodone (mean = 39.4 ng/mL; range, 1-256 ng/mL) by high-performance liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic modeling was performed using nonlinear mixed-effects modeling (NONMEM).


RESULTS
A one-compartment model with first-order absorption and elimination best described the data. Typical population values and between-subject variability (coefficient of variation, percent) for oxycodone clearance and the oral absorption rate constant were 73 L/h (31.9 %) and 0.0735 h (133 %), respectively. The volume of distribution was estimated based on literature values for intravenous oxycodone in cancer patients. The inclusion of weight, sex, age, creatinine clearance, and serum albumin concentration did not significantly explain pharmacokinetic variability in clearance or absorption rate constant. The subject with the most elevated liver function test values also had the lowest clearance per kilogram.


CONCLUSIONS
Oxycodone clearance was similar to that reported previously for healthy adults. Despite reports that patient characteristics significantly affect oxycodone pharmacokinetics, our results do not support alteration of current prescribing practices for maintenance dosing of Oxycontin® in most patients with advanced cancer. The influence of marked liver dysfunction on oxycodone clearance requires further investigation.
Bruce
B
Charles
Janet
J
Hardy
Helen
H
Anderson
Angela
A
Tapuni
Rani
R
George
Ross
R
Norris
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000097:blood / Q000378:metabolism*; D010098:Oxycodone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D010098:Oxycodone