Evaluation of the impact of Polygonum capitatum, a traditional Chinese herbal medicine, on rat hepatic cytochrome P450 enzymes by using a cocktail of probe drugs
Evaluation of the impact of Polygonum capitatum, a traditional Chinese herbal medicine, on rat hepatic cytochrome P450 enzymes by using a cocktail of probe drugs
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探针药物混合物评价头花蓼对大鼠肝细胞色素P450酶的影响
DOI：
10.1016/j.jep.2014.10.031
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发表时间：
2014-12-02
影响因子：
5.4
通讯作者：
Wang, Yong-Lin
中科院分区：
文献类型：
--
作者：
Zheng, Lin;Lu, Yuan;Wang, Yong-Lin
民族药理学相关性：头状蓼是一种著名的苗族药用植物，多年来一直被用于治疗各种泌尿系统疾病，包括尿路结石和尿路感染。采用“鸡尾酒”法，通过给予大鼠5种探针药物，研究了头状蓼在体内对细胞色素P450（CYP）亚型（CYP 1A 2、CYP 2C 9、CYP 2C 19、CYP 2 E1和CYP 3A 4）的影响。这项研究评估了潜在的头状蓼相互作用与共同管理的drugs.Materials和方法：制备干燥的全头状蓼的水提取物，并以0.58 g/kg或1.74 g/kg的剂量口服给大鼠，每天两次，连续7或14天。然后在第8天或第15天给予咖啡因（1.0 mg/kg）、甲苯磺丁脲（1.0 mg/kg）、奥美拉唑（2.0 mg/kg）、氯唑沙宗（4.0 mg/kg）和咪达唑仑（4.0 mg/kg）的鸡尾酒，以分别评价头花蓼对CYP 1A 2、2C 9、2C 19、2 E1和3A 4的影响。在一系列时间点收集血液样品，并使用超高效液相色谱-串联质谱法同时定量探针药物的血浆浓度。结果：何首乌预处理对咖啡因、奥美拉唑和氯唑沙宗的药代动力学参数无显著影响。结论：何首乌对CYP 1A 2、CYP 2C 19和CYP 2 E1无影响，但对CYP 2C 9和CYP 3A 4有诱导作用。因此，在服用何首乌的患者中，可能需要调整经人CYP 2C 9或CYP 3A 4代谢的药物的临床剂量，因为这种草药可能导致这些药物的有效浓度降低。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Polygonum capitatum is a well-known Miao medicinal plant that has been used for many years for its unique therapeutic effects on various urological disorders, including urinary calculus and urinary tract infections. To investigate the effect of Polygonum capitatum on cytochrome P450 (CYP) isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4) in vivo using a "cocktail" approach by administering five probe drugs to rats. This study assessed the potential of Polygonum capitatum to interact with co-administered drugs.Materials and methods: An aqueous extract of dried whole Polygonum capitatum was prepared and administered orally to rats at a dose of 0.58 g/kg or 1.74 g/kg twice daily for 7 or 14 consecutive days. A cocktail of caffeine (1.0 mg/kg), tolbutamide (1.0 mg/kg), omeprazole (2.0 mg/kg), chlorzoxazone (4.0 mg/kg) and midazolam (4.0 mg/kg) was then administered on the eighth or fifteenth day to evaluate the effects of Polygonum capitatum on CYP1A2, 2C9, 2C19, 2E1, and 3A4, respectively. Blood samples were collected at a range of time-points and the plasma concentrations of the probe drugs were simultaneously quantified using ultra high-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated to evaluate the effects of Polygonum capitatum on the activities of these CYP enzymes in rats.Results: Polygonum capitatum pre-treatment had no significant effect on the pharmacokinetic parameters of caffeine, omeprazole or chlorzoxazone. However, the pharmacokinetics of tolbutamide and midazolam were affected significantly (P < 0.05) by Polygonum capitatum, which induced more rapid metabolism of these probe compounds.Conclusions: These results suggested that Polygonum capitatum could induce CYP2C9 and CYP3A4, and did not influence CYP1A2, CYP2C19 or CYP2E1. Therefore, the clinical dose of drugs metabolized by human CYP2C9 or CYP3A4 may need to be adjusted in patients taking Polygonum capitatum, as this herbal medication may result in reduced effective concentrations of these drugs. (C) 2014 Elsevier Ireland Ltd. All rights reserved.