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Pharmacokinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions

Leuppi-Taegtmeyer, Anne and Duthaler, Urs and Hammann, Felix and Schmid, Yasmin and Dickenmann, Michael and Amico, Patricia and Jehle, Andreas W. and Kalbermatter, Stefan and Lenherr, Christoph and Meyer Zu Schwabedissen, Henriette E. and Haschke, Manuel and Liechti, Matthias E. and Krähenbühl, Stephan. (2018) Pharmacokinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 34 (4). pp. 692-702.

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Abstract

The pharmacokinetics of oxycodone in patients with end-stage renal disease (ESRD) requiring haemodialysis are largely unknown. Therefore, we investigated the pharmacokinetics of oxycodone/naloxone prolonged release and their metabolites in patients with ESRD during and between haemodialysis sessions.; Single doses of oxycodone/naloxone (5/2.5 or 10/5 mg) were administered in nine patients with ESRD using a cross-over design on the day of dialysis and on a day between dialysis sessions. Plasma, dialysate and urine concentrations of oxycodone, naloxone and their metabolites were determined up to 48 h post-dosing using a liquid chromatography-tandem mass spectrometry system.; Haemodialysis performed 6-10 h after dosing removed ∼10% of the administered dose of oxycodone predominantly as unconjugated oxycodone and noroxycodone or conjugated oxymorphone and noroxymorphone. The haemodialysis clearance of oxycodone based on its recovery in dialysate was (mean ± SD) 8.4 ± 2.1 L/h. The geometric mean (coefficient of variation) plasma elimination half-life of oxycodone during the 4-h haemodialysis period was 3.9 h (39%) which was significantly shorter than the 5.7 h (22%) without haemodialysis. Plasma levels of the active metabolite oxymorphone in its unconjugated form were very low.; Oxycodone is removed during haemodialysis. The pharmacokinetics including the relatively short half-life of oxycodone in patients with ESRD with or without haemodialysis and the absence of unconjugated active metabolites indicate that oxycodone can be used at usual doses in patients requiring dialysis.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Psychopharmacology Research (Liechti)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Liechti, Matthias Emanuel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:1460-2385
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:18 Apr 2019 14:28
Deposited On:18 Apr 2019 14:19

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