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

Leuppi-Taegtmeyer, Anne; Duthaler, Urs; Hammann, Felix; Schmid, Yasmin; Dickenmann, Michael; Amico, Patricia; Jehle, Andreas W; Kalbermatter, Stefan; Lenherr, Christoph; Meyer Zu Schwabedissen, Henriette E; Haschke, Manuel Martin; Liechti, Matthias E; Krähenbühl, Stephan (2019). Pharmacokinetics of oxycodone/naloxone and its metabolites in patients with end-stage renal disease during and between haemodialysis sessions. Nephrology, dialysis, transplantation, 34(4), pp. 692-702. Oxford University Press 10.1093/ndt/gfy285

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Background

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.

Methods

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.

Results

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.

Conclusions

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

UniBE Contributor:

Haschke, Manuel Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0931-0509

Publisher:

Oxford University Press

Language:

English

Submitter:

Tobias Tritschler

Date Deposited:

07 Feb 2019 15:48

Last Modified:

07 Sep 2021 17:17

Publisher DOI:

10.1093/ndt/gfy285

PubMed ID:

30189012

URI:

https://boris.unibe.ch/id/eprint/123182

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