Presented at the 2012 AAPM Annual Meeting « Back

Effect of Age and Sex on the Pharmacokinetics and Metabolism of Oxymorphone Extended-Release Tablets

Joseph V. Pergolizzi, MD, jpjmd@msn.com¹, Matthew Wieman, MD², Errol M. Gould, PhD², (1) Johns Hopkins University School of Medicine, Baltimore, Maryland, Naples, Florida, (2) Endo Pharmaceuticals Inc., Chadds Ford, Pennsylvania

Introduction: American Geriatrics Society guidelines recommend judicious use of opioid analgesics but note dosing requirements may change with age.1 This study evaluated effects of age and sex on the pharmacokinetics of oxymorphone extended release (ER). Materials and Methods: An open-label, parallel-group trial in four groups of healthy men and women designated as young (aged 18–40) or elderly (aged ≥65). Subjects received oxymorphone ER 20 mg once daily for 6 days and naltrexone 50 mg to minimize opioid effects. Plasma concentrations for oxymorphone and its 6-OH-oxymorphone and oxymorphone-3-glucuronide metabolites were analyzed. Institutional review board approval and subject informed consent were obtained. Results: 47 of 48 subjects completed the study. Mean (SD) steady-state area under the curve was higher in elderly subjects (men, 28.9 [11.4] ng/h/mL; women, 31.0 [15.9] ng/h/mL) than in young subjects (18.3 [4.9] ng/h/mL; 23.1 [7.9] ng/h/mL, respectively). Maximum concentrations were higher in elderly subjects (3.5 [1.4] ng/mL; 4.2 [2.7] ng/mL) versus young subjects (2.4 [0.7] ng/mL; 3.2 [1.1] ng/mL). Only age-based differences persisted after controlling for body weight. Similar results were observed for oxymorphone metabolites. Conclusions: Mean and maximum concentrations of oxymorphone and its metabolites were 35%–40% higher in elderly subjects. Initiating oxymorphone ER at a lower dose in elderly patients is advisable to minimize adverse events. References: 1)J Am Geriatr Soc. 2009;57(8):1331-46.

Funding: Supported by Endo Pharmaceuticals Inc., Chadds Ford, PA