TY - JOUR
T1 - Population pharmacokinetics of oxycodone and metabolites in patients with cancer‐related pain
AU - Agema, Bram C.
AU - Oosten, Astrid W.
AU - Sassen, Sebastiaan D.T.
AU - Rietdijk, Wim J.R.
AU - van der Rijt, Carin C.D.
AU - Koch, Birgit C.P.
AU - Mathijssen, Ron H.J.
AU - Koolen, Stijn L.W.
N1 - Funding Information:
The clinical study was financially supported by the Netherlands Organization for Health Research and Development (ZonMw project number 1151.0014), Cornelis Vrolijk Fund and Sticht-ing Voorzieningenfonds Palliatieve Zorg Dirksland.
Funding Information:
Funding: The clinical study was financially supported by the Netherlands Organization for Health Research and Development (ZonMw project number 1151.0014), Cornelis Vrolijk Fund and Sticht‐ ing Voorzieningenfonds Palliatieve Zorg Dirksland.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - Oxycodone is frequently used for treating cancer‐related pain, while not much is known about the factors that influence treatment outcomes in these patients. We aim to unravel these factors by developing a population‐pharmacokinetic model to assess the pharmacokinetics of oxycodone and its metabolites in cancer patients, and to associate this with pain scores, and adverse events. Hospitalized patients with cancer‐related pain, who were treated with oral oxycodone, could participate. Pharmacokinetic samples and patient‐reported pain scores and occurrence and severity of nine adverse events were taken every 12 h. In 28 patients, 302 pharmacokinetic samples were collected. A one‐compartment model for oxycodone and each metabolite best described oxycodone, nor‐oxycodone, and nor‐oxymorphone pharmacokinetics. Furthermore, oxycodone exposure was not associated with average and maximal pain scores, and oxycodone, nor-oxycodone, and nor‐oxymorphone exposure were not associated with adverse events (all p > 0.05). This is the first model to describe the pharmacokinetics of oxycodone including the metabolites nor-oxycodone and nor‐oxymorphone in hospitalized patients with cancer pain. Additional research, including more patients and a more timely collection of pharmacodynamic data, is needed to further elucidate oxycodone (metabolite) pharmacokinetic/pharmacodynamic relationships. This model is an important starting point for further studies to optimize oxycodone dosing regiments in patients with cancer‐related pain.
AB - Oxycodone is frequently used for treating cancer‐related pain, while not much is known about the factors that influence treatment outcomes in these patients. We aim to unravel these factors by developing a population‐pharmacokinetic model to assess the pharmacokinetics of oxycodone and its metabolites in cancer patients, and to associate this with pain scores, and adverse events. Hospitalized patients with cancer‐related pain, who were treated with oral oxycodone, could participate. Pharmacokinetic samples and patient‐reported pain scores and occurrence and severity of nine adverse events were taken every 12 h. In 28 patients, 302 pharmacokinetic samples were collected. A one‐compartment model for oxycodone and each metabolite best described oxycodone, nor‐oxycodone, and nor‐oxymorphone pharmacokinetics. Furthermore, oxycodone exposure was not associated with average and maximal pain scores, and oxycodone, nor-oxycodone, and nor‐oxymorphone exposure were not associated with adverse events (all p > 0.05). This is the first model to describe the pharmacokinetics of oxycodone including the metabolites nor-oxycodone and nor‐oxymorphone in hospitalized patients with cancer pain. Additional research, including more patients and a more timely collection of pharmacodynamic data, is needed to further elucidate oxycodone (metabolite) pharmacokinetic/pharmacodynamic relationships. This model is an important starting point for further studies to optimize oxycodone dosing regiments in patients with cancer‐related pain.
UR - http://www.scopus.com/inward/record.url?scp=85106984382&partnerID=8YFLogxK
U2 - 10.3390/cancers13112768
DO - 10.3390/cancers13112768
M3 - Article
AN - SCOPUS:85106984382
VL - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 11
M1 - 2768
ER -
