Herb-Drug Interactions: Challenges and Opportunities for Improved Predictions
Herb-Drug Interactions: Challenges and Opportunities for Improved Predictions
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DOI：
10.1124/dmd.113.055236
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发表时间：
2014-03-01
影响因子：
3.9
通讯作者：
Paine, Mary F.
中科院分区：
文献类型：
--
作者：
Brantley, Scott J.;Argikar, Aneesh A.;Paine, Mary F.
在早于书面记录的使用历史和“天然”确保安全的观念的支持下，草药产品越来越多地被纳入西方医疗保健中。消费者经常在不通知其医疗保健提供者的情况下自行服用这些产品和常规药物。当草药产品干扰药物代谢酶和/或转运蛋白的活性时，这种草药-药物组合可产生不利影响。尽管越来越多的认识这些类型的草药相互作用，相互作用的预测和评价的标准系统是不存在的。因此，草药-药物相互作用的机制仍然是药物治疗的一个未充分研究的领域。由于草药产品成分的可变性、致病成分的不确定性以及致病成分药代动力学的知识往往不足，因此草药产品相互作用责任的评估具有挑战性。这些局限性进一步被草药产品监管的不同观点所混淆。草药产品药物相互作用的系统性评价，是常规的新药开发，需要确定个别成分的草药产品和这些成分的相互作用潜力的特点。将这些信息整合到估计单个成分药代动力学的计算机模型中，应有助于前瞻性地识别草药-药物相互作用。这些概念是突出与示范草药产品奶蓟和白藜芦醇。这种方法的实施应有助于向消费者和临床医生提供关于在传统药物治疗方案中添加草药产品的风险的明确信息。
Supported by a usage history that predates written records and the perception that "natural" ensures safety, herbal products have increasingly been incorporated into Western health care. Consumers often self-administer these products concomitantly with conventional medications without informing their health care provider(s). Such herb-drug combinations can produce untoward effects when the herbal product perturbs the activity of drug metabolizing enzymes and/or transporters. Despite increasing recognition of these types of herb-drug interactions, a standard system for interaction prediction and evaluation is nonexistent. Consequently, the mechanisms underlying herb-drug interactions remain an understudied area of pharmacotherapy. Evaluation of herbal product interaction liability is challenging due to variability in herbal product composition, uncertainty of the causative constituents, and often scant knowledge of causative constituent pharmacokinetics. These limitations are confounded further by the varying perspectives concerning herbal product regulation. Systematic evaluation of herbal product drug interaction liability, as is routine for new drugs under development, necessitates identifying individual constituents from herbal products and characterizing the interaction potential of such constituents. Integration of this information into in silico models that estimate the pharmacokinetics of individual constituents should facilitate prospective identification of herb-drug interactions. These concepts are highlighted with the exemplar herbal products milk thistle and resveratrol. Implementation of this methodology should help provide definitive information to both consumers and clinicians about the risk of adding herbal products to conventional pharmacotherapeutic regimens.