Agema Bram C, Oosten Astrid W, Sassen Sebastiaan D T, Rietdijk Wim J R, van der Rijt Carin C D, Koch Birgit C P, Mathijssen Ron H J, Koolen Stijn L W
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, dr. Molewaterplein 40, 3015GD Rotterdam, The Netherlands.
Department of Clinical Pharmacy, Erasmus University Medical Center, dr. Molewaterplein 40, 3015GD Rotterdam, The Netherlands.
Cancers (Basel). 2021 Jun 2;13(11):2768. doi: 10.3390/cancers13112768.
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 > 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.
羟考酮常用于治疗癌症相关疼痛，但对于影响这些患者治疗效果的因素却知之甚少。我们旨在通过建立一个群体药代动力学模型来揭示这些因素，以评估羟考酮及其代谢产物在癌症患者中的药代动力学，并将其与疼痛评分及不良事件相关联。患有癌症相关疼痛且接受口服羟考酮治疗的住院患者可以参与。每12小时采集药代动力学样本以及患者报告的疼痛评分和9种不良事件的发生情况及严重程度。在28名患者中，共收集了302份药代动力学样本。一个用于羟考酮及其每种代谢产物的单室模型能最好地描述羟考酮、去甲羟考酮和去甲羟吗啡酮的药代动力学。此外，羟考酮暴露与平均疼痛评分和最大疼痛评分无关，且羟考酮、去甲羟考酮和去甲羟吗啡酮暴露与不良事件均无关联（所有P>0.05）。这是首个描述癌症疼痛住院患者中包括去甲羟考酮和去甲羟吗啡酮代谢产物在内的羟考酮药代动力学的模型。需要开展更多研究，包括纳入更多患者并更及时地收集药效学数据，以进一步阐明羟考酮（代谢产物）的药代动力学/药效学关系。该模型是进一步研究优化癌症相关疼痛患者羟考酮给药方案的重要起点。
