中国临床药理学杂志

补骨脂素和氯吡格雷对人肝微粒体中环泊酚代谢的影响

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路明 ¹ , 何文娟 ¹ , 尹晓玉 ² , 李文利 ¹ , 张甜甜 ¹ , 张志清 ¹

中国临床药理学杂志 | 研究方法 2025,41(11): 1608-1613

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中国临床药理学杂志 |研究方法 2025 , 41 (11) : 1608 -1613

补骨脂素和氯吡格雷对人肝微粒体中环泊酚代谢的影响

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路明¹, 何文娟¹, 尹晓玉², 李文利¹, 张甜甜¹, 张志清¹

作者信息

^1.河北医科大学第二医院药学部，河北石家庄 050000

^2.河北省人民医院药学部，河北石家庄 050051

通讯作者:

张志清，主任药师，硕士生导师 MP: 15803210627 E-mail: 26500007@hebmu.edu.cn

作者简介:

路明（1990-），男，主管药师，主要从事体内药物分析和药物相互作用的相关研究

Effects of psoralen and clopidogrel on the metabolism of ciprofol in human liver microsomes

Ming LU¹, Wen-juan HE¹, Xiao-yu YIN², Wen-li LI¹, Tian-tian ZHANG¹, Zhi-qing ZHANG¹

Affiliations

^1.Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China

^2.Department of Pharmacy, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China

出版时间: 2025-06-17 doi: 10.13699/j.cnki.1001-6821.2025.11.019

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摘要

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目的

探究补骨脂素和氯吡格雷对人肝微粒体中环泊酚代谢的影响。

方法

建立人肝微粒体孵育体系中环泊酚浓度的高效液相色谱串联质谱检测方法。考察该方法的专属性、标准曲线、定量下限、精密度、回收率、基质效应和稳定性。测定系列质量浓度的环泊酚与人肝微粒体共同孵育后的剩余量，并代入GraphPad Prism 8软件中计算得到环泊酚在人肝微粒体中的酶促反应动力学参数；将补骨脂素和氯吡格雷分别与环泊酚在孵育体系中共同孵育，计算得到2种细胞色素P450 2B6（CYP2B6）灭活药的半数抑制浓度（IC₅₀），进一步考察对环泊酚代谢的影响。

结果

环泊酚在1.00~100.00 μg·mL^-1呈线性关系，标准曲线方程为y=0.15x-0.11（r=0.999 2），定量下限为1.00 μg·mL^-1，批内及批间精密度的相对标准偏差小于7%，相对误差不超过±5%，回收率为92.69%～99.62%，基质效应在94.77%~101.84%，样品经37 ℃水浴2 h或室温放置8 h，处理后置于自动进样器24 h稳定性良好。环泊酚在人肝微粒体孵育体系中的米氏常数（K_m）为37.81 μg·mL^-1，最大反应速率（V_max）为41.54 ng·min^-1·mg protein^-1，固有清除率（CL_int）为0.91 mL·min^-1·mg^-1。补骨脂素和氯吡格雷对环泊酚的代谢呈剂量依赖性抑制作用，IC₅₀值分别为30.25和2.09 μmol·L^-1，表现出轻度和中度抑制作用。

结论

补骨脂素和氯吡格雷可降低人肝微粒体中环泊酚的代谢。

关键词

环泊酚 / 补骨脂素 / 氯吡格雷 / 药物相互作用 / 人肝微粒体

Abstract

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Objective

To explore the effects of psoralen and clopidogrel on metabolism of ciprofol in human liver microsomes.

Methods

A high performance liquid chromatography-tandem mass spectrometry method for the detection of ciprofol concentrations in human liver microsomes was established, and the specificity, linearity and lower limit of quantitation, precision, recovery rate, matrix effect and stability of this method were investigated. A series of remaining concentrations of ciprofol after co-incubation of with human liver microsomes were detected, and the results were substituted into GraphPad Prism 8 software to calculate the kinetic parameters of the enzymatic reaction of ciprofol in human liver microsomes. Afterwards, psoralen and clopidogrel were co-incubated with ciprofol, respectively, and the median inhibitory concentrations (IC₅₀) were calculated to investigate the effects of the two cytochrome P450 2B6 (CYP2B6) inactivators on ciprofol metabolism.

Results

Ciprofol was linear in the range of 1.00-100.00 μg·mL^-1. The standard curve equation was y=0.15x-0.11 (r=0.999 2); the lower limit of quantification was 1.00 μg·mL^-1. The relative standard deviation (RSD) values for intra-day and inter-day precision were less than 7%, with relative error not exceeding ±5%. The extraction recoveries and matrix effects were 92.69%-99.62% and 94.77%-101.84%, respectively. In addition, the samples exhibited satisfactory stabilities incubated in a water bath at 37 ℃ for 2 h, stored at room temperature for 8 h or processed and placed in the autosampler for 24 h. The Michaelis constant (K_m), maximum reaction rate (V_max) and intrinsic clearance (CL_int) of ciprofol were 37.81 μg·mL^-1, 41.54 ng·min^-1·mg protein^-1 and 0.91 mL·min^-1·mg^-1, respectively. Psoralen and clopidogrel inhibited the metabolism of ciprofol in human liver microsomes in a dose-dependent manner with IC₅₀ values of 30.25 and 2.09 μmol·L^-1, showing mild and moderate inhibition of the metabolism of ciprofol, respectively.

Conclusion

Psoralen and clopidogrel can reduce the metabolism of ciprofol in human liver microsomes.

Key words

ciprofol / psoralen / clopidogrel / drug-drug interactions / human liver microsomes

引用本文

路明, 何文娟, 尹晓玉, 李文利, 张甜甜, 张志清. 补骨脂素和氯吡格雷对人肝微粒体中环泊酚代谢的影响. 中国临床药理学杂志, 2025 , 41 (11) : 1608 -1613 . DOI: 10.13699/j.cnki.1001-6821.2025.11.019

Ming LU, Wen-juan HE, Xiao-yu YIN, Wen-li LI, Tian-tian ZHANG, Zhi-qing ZHANG. Effects of psoralen and clopidogrel on the metabolism of ciprofol in human liver microsomes[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (11) : 1608 -1613 . DOI: 10.13699/j.cnki.1001-6821.2025.11.019

基金

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河北省医学科学研究课题计划基金资助项目(20241993)

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2025年第41卷第11期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.11.019

接收时间：2024-12-01
首发时间：2026-08-04
出版时间：2025-06-17

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收稿日期：2024-12-01

基金

河北省医学科学研究课题计划基金资助项目(20241993)

作者信息

^1.河北医科大学第二医院药学部，河北石家庄 050000

^2.河北省人民医院药学部，河北石家庄 050051

通讯作者:

张志清，主任药师，硕士生导师 MP: 15803210627 E-mail: 26500007@hebmu.edu.cn

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.11.019

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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