Chen Feng, Li Li, Tian Dan-Dan
Hainan Provincial Key Laboratory of R&D of Tropical Herbs, School of Pharmacy, Hainan Medical College, Haikou 571199, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Biomed Res Int. 2017;2017:9868694. doi: 10.1155/2017/9868694. Epub 2017 Apr 3.
root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. This review summarized the effects of these bioactive components from roots on pharmacokinetics of comedicated drugs with mechanic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on the published data stemming from both and human studies. studies indicated that cytochrome P450 (CYP450), carboxylesterase enzyme, catechol--methyltransferase, organic anion transporter 1 (OAT1) and OAT3, and P-glycoprotein were the major targets involved in -drug interactions. Lipophilic tanshinones had much more potent inhibitory effects towards CYPs activities compared to hydrophilic phenolic acids, evidenced by much lower values of the former. Clinical -drug interaction studies were mainly conducted using CYP1A2 and CYP3A4 probe substrates. In addition, the effects of coexisting components on the pharmacokinetic behaviors of those noted bioactive compounds were also included herein.
丹参根在亚洲因其对心血管有益而被广泛使用,它含有亲水性酚酸和脂溶性丹参酮,人们认为这些成分是其治疗功效的原因。本综述基于已发表的动物和人体研究数据,总结了丹参根中这些生物活性成分对联合用药药代动力学的影响,并对蛋白质结合、酶活性和转运体活性改变的作用机制进行了深入分析。动物研究表明,细胞色素P450(CYP450)、羧酸酯酶、儿茶酚-O-甲基转移酶、有机阴离子转运体1(OAT1)和OAT3以及P-糖蛋白是参与药物相互作用的主要靶点。与亲水性酚酸相比,脂溶性丹参酮对CYPs活性的抑制作用更强,前者的IC50值低得多就证明了这一点。临床药物相互作用研究主要使用CYP1A2和CYP3A4探针底物进行。此外,本文还包括了共存成分对这些著名生物活性化合物药代动力学行为的影响。