Population Pharmacokinetics of Oxycodone and Metabolites in Patients with Cancer-Related Pain

SIMPLE SUMMARY: Patients with moderate to severe cancer-related pain are frequently treated with oxycodone, a strong-acting opioid. However, treatment with oxycodone does not always lead to sufficient analgesic action. In order to determine which factors affect treatment outcomes, we performed an observational study and developed a population pharmacokinetic model. The model described oxycodone, nor-oxycodone and nor-oxymorphone pharmacokinetics. The association between oxycodone or oxycodone metabolites’ exposure with pain scores and adverse events was not significant. The combined oxycodone, nor-oxycodone and nor-oxymorphone model is a good starting point for further unravelling the factors that affect the pharmacokinetic/pharmacodynamic relation of oxycodone and its metabolites. ABSTRACT: 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.