CYP3A5*3 Affects Plasma Disposition of Noroxycodone and Dose Escalation in Cancer Patients Receiving Oxycodone
CYP3A5*3 Affects Plasma Disposition of Noroxycodone and Dose Escalation in Cancer Patients Receiving Oxycodone
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DOI：
10.1177/0091270010388033
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发表时间：
2011-11-01
影响因子：
2.9
通讯作者：
Kawakami, Junichi
中科院分区：
文献类型：
--
作者：
Naito, Takafumi;Takashina, Yoshiaki;Kawakami, Junichi
本研究的目的是在接受羟考酮治疗的癌症患者中，基于CYP 2D 6、CYP 3A 5、ABCB 1和OPRM 1的遗传多态性，评价羟考酮及其去甲基化物的血浆处置和剂量递增。入选了62例接受羟考酮缓释片治疗的日本癌症患者。在滴定剂量下测定羟考酮、去甲羟考酮和羟吗啡酮的给药前血浆浓度（C-12）。每日羟考酮递增率被评价为阿片类药物递增指数（OEI）。遗传变异没有显著改变羟考酮C-12。CYP 2D 6快代谢者中的羟吗啡酮C-12及其与羟考酮C-12的比值显著高于中代谢者，但不影响剂量递增。相反，CYP 3A 5 *1携带者组中去甲羟考酮C-12及其与羟考酮C-12的比值显著高于 *3/*3组。CYP 3A 5 *3/*3组的OEI显著高于 *1携带者组。在其他遗传变异体中未观察到OEI的显著差异。剂量递增组的去甲羟考酮C-12高于非递增组，并显著影响剂量递增的发生率。总之，CYP 3A 5 *3改变了去甲羟考酮的血浆分布，这对接受羟考酮的癌症患者的剂量递增产生了相反的影响。
The aim of this study was to evaluate the plasma dispositions of oxycodone and its demethylates and dose escalation based on genetic polymorphisms of CYP2D6, CYP3A5, ABCB1, and OPRM1 in cancer patients receiving oxycodone. Sixty-two Japanese cancer patients receiving oxycodone extended-release tablets were enrolled. Predose plasma concentrations (C-12) of oxycodone, noroxycodone, and oxymorphone were determined at the titrated dose. Daily oxycodone escalation rate was evaluated as the opioid escalation index (OEI). Genetic variants did not significantly alter oxycodone C-12. Oxymorphone C-12 and its ratio to oxycodone C-12 were significantly higher in CYP2D6 extensive metabolizers than in intermediate metabolizers but did not affect dose escalation. In contrast, noroxycodone C-12 and its ratio to oxycodone C-12 were significantly higher in the CYP3A5*1 carrier group than in the *3/*3 group. The OEI was significantly higher in the CYP3A5*3/*3 group than in the *1 carrier group. No significant difference was observed in the OEI in the other genetic variants. Noroxycodone C-12 was higher in the dose escalation group as compared to the nonescalation group and significantly affected the incidence of dose escalation. In conclusion, CYP3A5*3 altered the plasma disposition of noroxycodone, which was inversely affecting the dose escalation in cancer patients receiving oxycodone.