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姜黄补充剂对乳腺癌患者紫杉醇药代动力学的影响:基于群体药代动力学方法的研究。

Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach.

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Chennai, Tamil Nadu, India.

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.

出版信息

Phytother Res. 2022 Apr;36(4):1761-1769. doi: 10.1002/ptr.7412. Epub 2022 Feb 18.

Abstract

Turmeric is one of the most used herbal supplements among cancer patients. It reportedly modulates the function of CYP450 enzymes and drug transporters. This study investigates the effect of turmeric on the pharmacokinetics of paclitaxel in breast cancer patients. This is a prospective longitudinal study with 60 breast cancer patients on treatment with single-agent paclitaxel and turmeric. The patients were followed up for two consecutive chemotherapy cycles, and their blood samples were collected, first without turmeric (first cycle) and the next after a 21-day concomitant administration of 2 g/day turmeric (second cycle). Plasma samples were quantified for paclitaxel concentration using High Performance Liquid Chromatograph with UV detector (HPLC-UV) method. The sparse concentration-time data of paclitaxel were subjected to population pharmacokinetic modeling, and then noncompartmental analysis (NCA) was performed on the simulated data to estimate the pharmacokinetic parameters of paclitaxel, before and after turmeric supplementation, for comparisons. The population pharmacokinetic parameters of paclitaxel differed from before to after turmeric supplementation. NCA of simulated concentration-time profiles showed a statistically significant reduction of 7.7% and 12.1% in AUC and Cmax, respectively. Given the small magnitude of the changes in pharmacokinetic parameters, the observed changes are not clinically relevant. Thereby, turmeric at the recommended dose can be combined safely with paclitaxel.

摘要

姜黄是癌症患者最常使用的草药补充剂之一。据报道,它可调节 CYP450 酶和药物转运体的功能。本研究调查了姜黄对乳腺癌患者紫杉醇药代动力学的影响。这是一项前瞻性纵向研究,纳入了 60 名接受单药紫杉醇和姜黄治疗的乳腺癌患者。这些患者接受了两个连续化疗周期的随访,采集了他们的血样,第一次是没有姜黄的(第一周期),第二次是在第 21 天同时给予 2g/天姜黄后(第二周期)。使用高效液相色谱-紫外检测法(HPLC-UV)对血浆样本中的紫杉醇浓度进行定量。采用群体药代动力学模型对紫杉醇稀疏浓度-时间数据进行分析,然后对模拟数据进行非房室分析(NCA),以估算姜黄补充前后紫杉醇的药代动力学参数,并进行比较。姜黄补充前后紫杉醇的群体药代动力学参数有所不同。模拟浓度-时间曲线的 NCA 显示 AUC 和 Cmax 分别降低了 7.7%和 12.1%,差异具有统计学意义。鉴于药代动力学参数变化幅度较小,观察到的变化无临床意义。因此,推荐剂量的姜黄可与紫杉醇安全联合使用。

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