Drugs & Aging

, Volume 28, Issue 1, pp 41–50

Elimination of Intravenous Oxycodone in the Elderly

A Pharmacokinetic Study in Postoperative Orthopaedic Patients of Different Age Groups
  • Antti Liukas
  • Kristiina Kuusniemi
  • Riku Aantaa
  • Petri Virolainen
  • Mikko Neuvonen
  • Pertti J. Neuvonen
  • Klaus T. Olkkola
Original Research Article

Abstract

Background and Objective: Oxycodone is a widely used opioid analgesic, the global use of which has increased several-fold during the last decade. This study was designed to determine the effect of age on the pharmacokinetics of intravenous oxycodone, with special reference to renal function in elderly patients.

Methods: We compared the pharmacokinetics of 5 mg of intravenous oxycodone in four groups of 10–11 patients, aged 20–40, 60–70, 70–90 years, undergoing orthopaedic surgery. Plasma concentrations of oxycodone and its noroxycodone, oxymorphone and noroxymorphone metabolites were measured for 24 hours with a liquid chromatography-tandem mass spectrometric method. The cytochrome P450 (CYP) 2D6 genotype of the patients was determined. Glomerular filtration rate (GFR) was estimated on the basis of the age, sex and serum creatinine concentration of the patient.

Results: The pharmacokinetics of oxycodone showed age dependency. In the oldest group, the mean area under the plasma concentration-time curve from time zero to infinity (AUC∞) of oxycodone was 80% greater (p < 0.001) and the apparent total body clearance of the drug from plasma (CL) was 34% lower (p < 0.05) than in the youngest group. The mean AUC∞ of oxycodone was also 30–41% greater in the oldest group than in the age groups of 60–70 and 70–80 years (p < 0.05). Oxycodone plasma concentrations from 8 hours post-dose were >2-fold higher (p < 0.01) in patients aged >80 years than in patients aged 20–40 years. Noroxycodone AUC∞ was increased in the oldest group compared with patients aged 20–40 and 60–70 years (p < 0.05). There were no significant sex-related differences in any of the pharmacokinetic parameters. Because 37 of the 41 patients were extensive metabolizers through CYP2D6, the effect of the CYP2D6 genotype on oxycodone pharmacokinetics could not be properly assessed. There was a linear correlation between GFR and CL (p < 0.01, coefficient of determination [r2] = 0.26), volume of distribution at steady state (p < 0.05, r2 = 0.19) and AUC∞ (p < 0.01, r2 = 0.29) of oxycodone.

Conclusions: Age is an important factor affecting the pharmacokinetics of oxycodone. Following intravenous administration of oxycodone, patients aged >70 years are expected to have, on average, 40–80% higher exposure to oxycodone than young adult patients. Because oxycodone pharmacokinetics are greatly dependent on the age of the patient, it is important to titrate the analgesic dose individually, particularly in the elderly.

References

  1. 1.
    Kalso E, Vainio A. Morphine and oxycodone hydrochloride in the management of cancer pain. Clin Pharmacol Ther 1990; 47: 631–46CrossRefGoogle Scholar
  2. 2.
    Kalso E, Pöyhiä R, Onnela P, et al. Oxycodone and morphine in postoperative pain. Acta Anaesthesiol Scand 1991; 35: 642–6PubMedCrossRefGoogle Scholar
  3. 3.
    Saari TI, Grönlund J, Hagelberg NM, et al. Effects of itraconazole on the pharmacokinetics and pharmacodynamics of intravenously and orally administered oxycodone. Eur J Clin Pharmacol 2010; 66: 387–97PubMedCrossRefGoogle Scholar
  4. 4.
    Pöyhiä R, Seppälä T, Olkkola KT, et al. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol 1992; 33: 617–21PubMedCrossRefGoogle Scholar
  5. 5.
    Leow KP, Smith MT, Watt JA, et al. Comparative oxycodone pharmacokinetics in humans after intravenous, oral and rectal administration. Ther Drug Monit 1992; 14: 479–84PubMedCrossRefGoogle Scholar
  6. 6.
    Leow KP, Smith M, Williams BE, et al. Single dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. Clin Pharmacol Ther 1992; 52: 487–95PubMedCrossRefGoogle Scholar
  7. 7.
    Paulozzi LJ. Opioid analgesic involvement in drug abuse deaths in American metropolitan areas. Am J Public Health 2006; 96: 1755–7PubMedCrossRefGoogle Scholar
  8. 8.
    Heiskanen T, Olkkola KT, Kalso E. Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther 1998; 64: 603–11PubMedCrossRefGoogle Scholar
  9. 9.
    Lalovic B, Kharasch E, Hoffer C, et al. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites. Clin Pharmacol Ther 2006; 79: 461–79PubMedCrossRefGoogle Scholar
  10. 10.
    El-Tahtawy A, Kokki H, Reidenberg BE. Population pharmacokinetics of oxycodone in children 6 months to 7 years old. J Clin Pharmacol 2006; 46: 433–42PubMedCrossRefGoogle Scholar
  11. 11.
    Kokki H, Rasanen I, Reinikainen M, et al. Pharmacokinetics of oxycodone after intravenous, buccal, intramuscular and gastric administration in children. Clin Pharmacokinet 2004; 43: 613–22PubMedCrossRefGoogle Scholar
  12. 12.
    Olkkola KT, Hamunen K, Seppälä T, et al. Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children. Br J Clin Pharmacol 1994; 38: 71–6PubMedCrossRefGoogle Scholar
  13. 13.
    Pokela M-L, Anttila E, Seppälä T, et al. Marked variation in oxycodone pharmacokinetics in infants. Pediatr Anesth 2005; 15: 560–5CrossRefGoogle Scholar
  14. 14.
    Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin Pharmacol Ther 2007; 82: 87–96PubMedCrossRefGoogle Scholar
  15. 15.
    Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139: 137–47PubMedGoogle Scholar
  16. 16.
    Neuvonen M, Neuvonen PJ. Determination of oxycodone, noroxycodone, oxymorphone, and noroxymorphone in human plasma by liquid chromatography-electrospray-tandem mass spectrometry. Ther Drug Monit 2008; 30: 333–40PubMedCrossRefGoogle Scholar
  17. 17.
    Sistonen J, Fuselli S, Levo A, et al. CYP2D6 genotyping by a multiplex primer extension reaction. Clin Chem 2005; 51: 1291–5PubMedCrossRefGoogle Scholar
  18. 18.
    Liukas A, Kuusniemi K, Aantaa R, et al. Plasma concentrations of oral oxycodone are greatly increased in the elderly. Clin Pharmacol Ther 2008; 84: 462–7PubMedCrossRefGoogle Scholar
  19. 19.
    Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009; 41: 67–76PubMedCrossRefGoogle Scholar
  20. 20.
    Shi S, Mörike K, Klotz U. The clinical implications of ageing for rational drug therapy. Eur J Clin Pharmacol 2008; 64: 183–99PubMedCrossRefGoogle Scholar
  21. 21.
    Kirvelä M, Lindgren L, Seppälä T, et al. The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth 1996; 8: 13–8PubMedCrossRefGoogle Scholar
  22. 22.
    Kaiko R, Benziger D, Cheng C, et al. Clinical pharmacokinetics of controlled release oxycodone in renal impairment [abstract]. Clin Pharmacol Ther 1996; 59: 130Google Scholar
  23. 23.
    Purdue Pharma prescribing information on Oxycontin (oxycodone HCl controlled-release) tablets [online]. Available from URL: http://www.purduepharma.com/PI/Prescription/Oxycontin.pdf [Accessed 2010 Apr 21]
  24. 24.
    Zwisler ST, Enggaard TP, Mikkelsen S, et al. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia. Acta Anaesthesiol Scand 2010; 54: 232–40PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Antti Liukas
    • 1
  • Kristiina Kuusniemi
    • 1
  • Riku Aantaa
    • 1
  • Petri Virolainen
    • 2
  • Mikko Neuvonen
    • 3
  • Pertti J. Neuvonen
    • 3
  • Klaus T. Olkkola
    • 1
  1. 1.Department of Anesthesiology, Intensive Care, Emergency Care and Pain MedicineUniversity of Turku and Turku University HospitalTurkuFinland
  2. 2.Department of Orthopedics and TraumatologyUniversity of Turku and Turku University HospitalTurkuFinland
  3. 3.Department of Clinical PharmacologyUniversity of Helsinki and Helsinki University Central HospitalHelsinkiFinland

Personalised recommendations