Abstract
Simple SummaryPatients 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.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.
Highlights
Pain is the most common symptom in cancer patients and its incidence increases with disease progression
All patients treated with oxycodone were eligible, i.e., patients already treated with oxycodone before admission and opioid-naïve patients or patients rotating to oxycodone after failure of treatment with another opioid
302 pharmacokinetic samples for oxycodone and its metabolites were available for analysis from 28 patients
Summary
Pain is the most common symptom in cancer patients and its incidence increases with disease progression. Oxycodone is a widely used strong-acting opioid-agonist and is available in immediaterelease (IR) and extended-release (ER) formulations. This combination is practical in treating both chronic and breakthrough pain with the same drug. Pain relief and the occurrence of adverse events vary largely between patients [1,2]. Because of the variation in both pain relief and the occurrence of adverse events, clinical practice mostly consists of dose-titration until either sufficient analgesic effect is achieved or dose-limiting adverse events occur [3]. In case of insufficient pain control and/or dose-limiting adverse events, opioid rotation is indicated. This process is conducted on an empirical basis for each patient and is often time consuming
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