Boaz Gedaliahu Samolsky Dekel1,2,3, Gabriele Donati4,5, Alessio Vasarri2,3, Anna Laura Croci Chiocchini4,5, Alberto Gori2,3, Giuseppe Cavallari4,5, Gianfranco Di Nino1,2,3, Laura Mercolini6, Michele Protti6, Roberto Mandrioli7, Rita Maria Melotti1,2,3, Gaetano La Manna1,4,5. 1. Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy. 2. Anesthesiology and Intensive Care Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy. 3. Post Graduate School of Anaesthesia and Intensive Care, University of Bologna, Bologna, Italy. 4. Nephrology, Dialysis and Renal Transplant Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy. 5. Post Graduate School of Nephrology, University of Bologna, Bologna, Italy. 6. Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. 7. Department for Life Quality Studies, University of Bologna, Rimini, Italy.
Abstract
OBJECTIVES: Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking. METHODS: We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis. RESULTS: Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. DISCUSSION: While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.
OBJECTIVES: Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking. METHODS: We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic painpatients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis. RESULTS: Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. DISCUSSION: While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.
Authors: William C Becker; Michael J Fischer; Daniel G Tobin; Mark B Lockwood; Paul L Kimmel; Laura M Dember; Nwamaka D Eneanya; Manisha Jhamb; Thomas D Nolin Journal: Nat Rev Nephrol Date: 2021-10-07 Impact factor: 28.314