Evaluation of potential herbal-drug interactions of a standardized propolis extract (EPP-AF®) using an in vivo cocktail approach
Evaluation of potential herbal-drug interactions of a standardized propolis extract (EPP-AF®) using an in vivo cocktail approach
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DOI：
10.1016/j.jep.2019.112174
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发表时间：
2019-12-05
影响因子：
5.4
通讯作者：
Coelho, Eduardo B.
中科院分区：
文献类型：
--
作者：
Cusinato, Diego A. C.;Martinez, Edson Z.;Coelho, Eduardo B.
民族药理学相关性：蜂胶由于其生物学和药理学特性，如免疫调节、抗肿瘤、抗炎、抗氧化、抗菌、抗病毒、抗真菌、抗寄生虫活性，自古以来就被广泛用于许多文化中作为防腐剂、伤口愈合、解热和其他。但是，尽管其广泛和传统的使用，有很少的知识，其潜在的相互作用与处方药物。目的的研究：这项工作的主要目的是研究潜在的草药药物相互作用（HDI）的EPP-AF（R）使用体内试验与cocktail approach.Materials和方法：亚治疗剂量的咖啡因，氯沙坦，奥美拉唑，美托洛尔，咪达唑仑和非索非那定。16名健康成年志愿者在暴露于口服125 mg/8 h（375 mg/天）EPP-AF（R）15天之前和之后进行了研究。基于血浆浓度-时间（AUC）曲线计算药代动力学参数。暴露于EPP-AP（R）后，观察到AUC降低（0-无穷大）非索非那定、咖啡因和氯沙坦约为18%（62.20 x 51.00 h.ng/mL）、8%（1085 x 999 h.ng/mL）和13%（9.01 x 7.86 h.ng/mL），所有90% CI均在0.80-1.25的等效范围内。另一方面，奥美拉唑和咪达唑仑的AUC（0-无穷大）分别增加约18%（18.90 x 22.30 h.ng/mL）和14%（1.25 x 1.43 h.ng/mL），90% CI上限略高于1.25。美托洛尔或其代谢产物α-羟基美托洛尔的药代动力学变化无统计学意义，其90%CI在0.80- 1.25的等效范围内。总之，我们的研究表明，EPP-AF（R）不会在临床上改变CYP 1A 2、CYP 2C 9、CYP 2C 19、CYP 2D 6和CYP 3A活性，尽管具有统计学显著性，EPP-AF（R）后AUC值的变化幅度均低于20%，因此，就涉及这些酶的潜在相互作用而言，可以认为是安全的。此外，据我们所知，这是第一项评估潜在HDIs的研究。
Ethnopharmacological relevance: Propolis has been employed extensively in many cultures since ancient times as antiseptic, wound healing, anti-pyretic and others due to its biological and pharmacological properties, such as immunomodulatory, antitumor, anti-inflammatory, antioxidant, antibacterial, antiviral, antifungal, antiparasite activities. But despite its broad and traditional use, there is little knowledge about its potential interaction with prescription drugs.Aim of the study: The main objective of this work was to study the potential herbal-drug interactions (HDIs) of EPP-AF (R) using an in vivo assay with a cocktail approach.Materials and methods: Subtherapeutic doses of caffeine, losartan, omeprazole, metoprolol, midazolam and fexofenadine were used. Sixteen healthy adult volunteers were investigated before and after exposure to orally administered 125 mg/8 h (375 mg/day) EPP-AF (R) for 15 days. Pharmacokinetic parameters were calculated based on plasma concentration versus time (AUC) curves.Results: After exposure to EPP-AP (R), it was observed decrease in the AUC(0-infinity) of fexofenadine, caffeine and losartan of approximately 18% (62.20 x 51.00 h.ng/mL), 8% (1085 x 999 h.ng/mL) and 13% (9.01 x 7.86 h.ng/mL), respectively, with all 90% CIs within the equivalence range of 0.80-1.25. On the other hand, omeprazole and midazolam exhibited an increase in AUC(0-infinity) of, respectively, approximately 18% (18.90 x 22.30 h.ng/mL) and 14% (1.25 x 1.43 h.ng/mL), with the upper bounds of 90% CIs slightly above 1.25. Changes in pharmacokinetics of metoprolol or its metabolite alpha-hydroxymetoprolol were not statistically significant and their 90% CIs were within the equivalence range of 0.80-1.25.Conclusions: In conclusion, our study shows that EPP-AF (R) does not clinically change CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A activities, once, despite statistical significant, the magnitude of the changes in AUC values after EPP-AF (R) were all below 20% and therefore may be considered safe regarding potential interactions involving these enzymes. Besides, to the best of our knowledge this is the first study to assess potential HDIs with propolis.