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Influences of phytocannabinoids on drug-drug interactions and their clinical implications.
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.pharmthera.2020.107621
Daniela Amaral Silva 1 , David W Pate 2 , Robert D Clark 3 , Neal M Davies 1 , Ayman O S El-Kadi 1 , Raimar Löbenberg 1
Affiliation  

Cannabis is a plant with a long history of human pharmacological use, both for recreational purposes and as a medicinal remedy. Many potential modern medical applications for cannabis have been proposed and are currently under investigation. However, its rich chemical content implies many possible physiological actions. As the use of medicinal cannabis has gained significant attention over the past few years, it is very important to understand phytocannabinoid dispositions within the human body, and especially their metabolic pathways. Even though the complex metabolism of phytocannabinoids poses many challenges, a more thorough understanding generates many opportunities, especially regarding possible drug-drug interactions (DDIs). Within this context, computer simulations are most commonly used for predicting substrates and inhibitors of metabolic enzymes. These predictions can assist to identify metabolic pathways by understanding individual CYP isoform specificities to a given molecule, which can help to predict potential enzyme inhibitions and DDIs. The reported in vivo Phase I and Phase II metabolisms of various phytocannabinoids is herein reviewed, accompanied by a parallel in silico analysis of their predicted metabolism, highlighting the clinical importance of such understanding in terms of DDIs and clinical outcomes.



中文翻译:

植物大麻素对药物-药物相互作用的影响及其临床意义。

大麻是一种具有悠久历史的人类药理学用途的植物,既可用于娱乐目的,也可用作药物。已经提出了许多潜在的大麻现代医学应用,目前正在调查中。然而,其丰富的化学成分意味着许多可能的生理作用。由于药用大麻的使用在过去几年中受到了极大的关注,因此了解人体内植物大麻素的分布,尤其是它们的代谢途径非常重要。尽管植物大麻素的复杂代谢带来了许多挑战,但更深入的了解会产生许多机会,尤其是在可能的药物相互作用 (DDI) 方面。在此背景下,计算机模拟最常用于预测代谢酶的底物和抑制剂。这些预测可以通过了解给定分子的个体 CYP 亚型特异性来帮助识别代谢途径,这有助于预测潜在的酶抑制和 DDI。报道的本文回顾了各种植物大麻素的体内I 期和 II 期代谢,同时对其预测代谢进行了并行计算机分析,突出了这种理解在 DDI 和临床结果方面的临床重要性。

更新日期:2020-07-20
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