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影响羟考酮药代动力学的因素：439 例成年癌症患者的多中心横断面研究。

Influences on the pharmacokinetics of oxycodone: a multicentre cross-sectional study in 439 adult cancer patients.

机构信息

Pain and Palliation Research Group, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

出版信息

Eur J Clin Pharmacol. 2011 May;67(5):493-506. doi: 10.1007/s00228-010-0948-5. Epub 2010 Dec 8.

DOI:10.1007/s00228-010-0948-5
PMID:21140139
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3076582/
Abstract

OBJECTIVE

Oxycodone is widely used for the treatment of cancer pain, but little is known of its pharmacokinetics in cancer pain patients. The aim of this study was to explore the relationships between ordinary patient characteristics and serum concentrations of oxycodone and the ratios noroxycodone or oxymorphone/oxycodone in cancer patients.

METHODS

Four hundred and thirty-nine patients using oral oxycodone for cancer pain were included. The patients' characteristics (sex, age, body mass index [BMI], Karnofsky performance status, "time since starting opioids", "oxycodone total daily dose", "time from last oxycodone dose", use of CYP3A4 inducer/inhibitor, "use of systemic steroids", "number of medications taken in the last 24 h", glomerular filtration rate (GFR) and albumin serum concentrations) influence on oxycodone serum concentrations or metabolite/oxycodone ratios were explored by multiple regression analyses.

RESULTS

Sex, CYP3A4 inducers/inhibitors, total daily dose, and "time from last oxycodone dose" predicted oxycodone concentrations. CYP3A4 inducers, total daily dose, and "number of medications taken in the last 24 h" predicted the oxymorphone/oxycodone ratio. Total daily dose, "time from last dose to blood sample", albumin, sex, CYP3A4 inducers/inhibitors, steroids, BMI and GFR predicted the noroxycodone/oxycodone ratio.

CONCLUSION

Women had lower oxycodone serum concentrations than men. CYP3A4 inducers/inhibitors should be used with caution as these are predicted to have a significant impact on oxycodone pharmacokinetics. Other characteristics explained only minor parts of the variability of the outcomes.

摘要

目的

羟考酮被广泛用于治疗癌痛，但关于其在癌痛患者中的药代动力学特性知之甚少。本研究旨在探讨普通患者特征与羟考酮血清浓度及去甲羟考酮或羟吗啡酮/羟考酮比值之间的关系。

方法

纳入 439 例使用口服羟考酮治疗癌痛的患者。通过多元回归分析探讨了患者特征（性别、年龄、体重指数[BMI]、卡氏功能状态评分、“开始使用阿片类药物的时间”、“羟考酮总日剂量”、“上次服用羟考酮的时间”、是否使用 CYP3A4 诱导剂/抑制剂、“是否使用全身皮质类固醇”、“过去 24 小时内使用的药物数量”、肾小球滤过率（GFR）和白蛋白血清浓度）对羟考酮血清浓度或代谢物/羟考酮比值的影响。

结果

性别、CYP3A4 诱导剂/抑制剂、总日剂量和“上次服用羟考酮的时间”预测了羟考酮浓度。CYP3A4 诱导剂、总日剂量和“过去 24 小时内使用的药物数量”预测了羟吗啡酮/羟考酮比值。总日剂量、“上次服用羟考酮至采血的时间”、白蛋白、性别、CYP3A4 诱导剂/抑制剂、皮质类固醇、BMI 和 GFR 预测了去甲羟考酮/羟考酮比值。

结论

女性的羟考酮血清浓度低于男性。CYP3A4 诱导剂/抑制剂的使用应谨慎，因为它们可能对羟考酮的药代动力学有显著影响。其他特征仅能解释部分结果的变异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/cdb668ac71e7/228_2010_948_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/8b140878a1fe/228_2010_948_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/3a06c2fd7472/228_2010_948_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/f2db1dde4c40/228_2010_948_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/82228d200c9d/228_2010_948_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/cdb668ac71e7/228_2010_948_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/8b140878a1fe/228_2010_948_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/3a06c2fd7472/228_2010_948_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/f2db1dde4c40/228_2010_948_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/82228d200c9d/228_2010_948_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8676/3076582/cdb668ac71e7/228_2010_948_Fig5_HTML.jpg

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