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Pharmacokinetics of intravenous oxycodone hydrochloride in perioperative patients with liver cancer
Shuwei Shi1,2, Ying Zheng1,2, Yong Wang3
1Pharmacy Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Introduction:
Effective perioperative analgesia in liver cancer patients presents an ongoing clinical challenge. This study investigates oxycodone's pharmacokinetics in perioperative liver cancer patients with normal liver function to support individualized analgesia.
Methods:
This study developed and validated a reliable high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous quantification of oxycodone and its metabolite noroxycodone in human plasma. The method was successfully applied to characterize the pharmacokinetics in nine surgical liver cancer patients following intravenous oxycodone administration, using non-compartmental analysis (NCA).
Results:
The developed method showed satisfactory linearity and met validation criteria. In perioperative liver cancer patients, oxycodone exhibited reduced clearance, prolonged half-life, increased volume of distribution, and elevated exposure compared with healthy volunteers. Its metabolite noroxycodone displayed a biphasic profile with consistently higher concentrations in males. Significant sex-related differences were also observed for oxycodone's area under the plasma concentration-time curve (AUC) and mean residence time (MRT).
Discussion:
This study reveals that compared with healthy volunteers, perioperative liver cancer patients with normal liver function exhibit significantly altered oxycodone pharmacokinetics, including reduced clearance, prolonged half-life, increased exposure and volume of distribution, with notable sex differences. These findings support the need for dose reduction, extended monitoring, and individualized analgesic strategies.
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