Pharmacokinetics of morphine and oxycodone following intravenous administration in elderly patients

Hanne H Villesen¹, Anne-Marie Banning², Rasmus H Petersen³, Sebatian Weinelt³, Jesper B Poulsen³, Steen H Hansen⁴, Lona L Christrup^1
1Department of Pharmacology and Pharmacotherapy, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark; ²Department  of Anesthesiology, Gentofte University Hospital, Copenhagen, Denmark; ³Department of Anesthesiology, Esbjerg Hospital, Esbjerg, Denmark;⁴Department of Pharmaceutics and Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Copenhagen, Denmark

Background: An increased and prolonged duration of pain relief after morphine administration has been found in elderly patients. Whether this is due to alterations in pharmacokinetics, receptor binding profile or other factors remains unsolved. The aims were to elucidate the pharmacokinetics after intravenous administration of morphine and oxycodone in elderly patients older than 70 years.

Methods: A randomized non-blinded study with 16 patients aged older than 70 years scheduled for elective hip replacement receiving morphine or oxycodone 0.05 mg/kg as an IV infusion over 15 minutes.

Results: A 2-compartment pharmacokinetic model best described the disposition of morphine and oxycodone. The estimated elimination half-lives for morphine and oxycodone were (mean ± SD) 2.7 ± 3.6 (range 0.8–11.6) and 3.1 ± 1.3 (range 1.1–4.8) hr, respectively. Volume of distribution at steady state was estimated to be 243 ± 256 and 277 ± 187 L, and clearance to be 1748 ± 623 and 1206 ± 546 ml/min for morphine and oxycodone, respectively.

Conclusion: The increased and prolonged duration of pain relief after morphine administration seen in some elderly patients cannot, based on these findings, be ascribed to changes in the pharmacokinetic parameters between elderly and younger patients. Similar for oxycodone, no changes in the pharmacokinetic could be found when comparing the parameters found in elderly patients with those from younger healthy volunteers. A great variability within the individual pharmacokinetic parameters was seen for both drugs. Therefore, we recommend that treatment with morphine and oxycodone in elderly patients is initiated very conservatively and is titrated slowly to effect.

Keywords: morphine, oxycodone, pharmacokinetics, age, elderly

A Letter to the Editor has been received and published for this article.