Sevior D K, Hokkanen J, Tolonen A, Abass K, Tursas L, Pelkonen O, Ahokas J T
RMIT Toxicology, RMIT University, Plenty Road, Bundoora, Victoria 3083, Australia.
Xenobiotica. 2010 Apr;40(4):245-54. doi: 10.3109/00498251003592683.
Self-administration of complementary products concurrently with conventional medication is increasingly common. The potential for cytochrome P450 (CYP) inhibition requires investigation. The N-in-one assay with ten probe substrates for nine CYPs was used with human liver microsomes to investigate ten products. CYP inhibition was measured in a single liquid chromatography-tandem mass spectrometry (LC/MS-MS) analysis. Estimated IC(50)-values were determined for the extracts that produced significant inhibition (less than 100 microg ml(-1)). Inhibition of CYP2C19 by dong quai (IC(50) = 13.7-14.3 microg ml(-1) for the methanolic extract) and CYP2D6 by goldenseal (IC(50) = 6.7 and 6.3 microg ml(-1) for the aqueous and methanolic extracts, respectively), are of particular concern as the potential for adverse interactions is high. The inhibition of CYP2C8 by horsetail (IC(50) = 93 microg ml(-1) for the aqueous extract) requires further investigation, as the potential for concurrent use with products that require CYP2C8 for metabolism is significant. CYP3A4 inhibition varied depending on the probe reaction being monitored. The earlier reported findings of inhibition by black cohosh, goldenseal and gotu kola were confirmed. The present work has shown that the N-in-one cocktail is a rapid and reliable method that can be used as an initial screen to help prioritize products that require more detailed investigations and it can also be applied to monitor product variability.
在服用传统药物的同时自行服用补充剂的情况越来越普遍。细胞色素P450（CYP）抑制的可能性需要进行研究。使用针对9种CYP的10种探针底物的“N合一”测定法，结合人肝微粒体来研究10种产品。通过单次液相色谱 - 串联质谱（LC/MS-MS）分析来测量CYP抑制作用。对于产生显著抑制作用（小于100μg ml⁻¹）的提取物，测定其估计的IC₅₀值。当归对CYP2C19的抑制作用（甲醇提取物的IC₅₀ = 13.7 - 14.3μg ml⁻¹）以及白毛茛对CYP2D6的抑制作用（水提取物和甲醇提取物的IC₅₀分别为6.7和6.3μg ml⁻¹）尤其值得关注，因为发生不良相互作用的可能性很高。木贼对CYP2C8的抑制作用（水提取物的IC₅₀ = 93μg ml⁻¹）需要进一步研究，因为与需要CYP2C8进行代谢的产品同时使用的可能性很大。CYP3A4的抑制作用因所监测的探针反应而异。 earlier reported findings of inhibition by black cohosh, goldenseal and gotu kola were confirmed. 目前的研究表明，“N合一”混合物是一种快速可靠的方法，可作为初步筛选，帮助确定需要更详细研究的产品的优先级，并且还可用于监测产品的变异性。 （注：原文中“earlier reported findings of inhibition by black cohosh, goldenseal and gotu kola were confirmed.”这部分英文表述似乎有误，可能影响对整体内容的理解，但按照要求仅进行字面翻译。）
