肠道菌介导的PK-PD新模式:小檗碱药代动力学引发的思考

A new research mode of drug PK-PD mediated by the gut microbiota: insights into the pharmacokinetics of berberine

小檗碱(berberine)是近年来研究最多的我国原创天然药物之一,是具有与他汀完全不同机制的新的降血脂药物,疗效在临床被证实。但是,小檗碱口服后在肠道吸收较差,其血中暴露量低、生物利用度小于5%的药代数据很难解释它在体内的疗效。实际上,这种现象也出现在多个临床有效的天然药物中,具有普遍的科学意义。本文介绍了新近研究发现的小檗碱的药代特点,着重介绍肠道菌在小檗碱药代中的重要作用。同时,还以小檗碱的研究结果为例,对经典药代的内容进行了讨论,强调肠道菌对口服化学药物的药代动力学的重要影响,提出肠道菌介导的药物PK-PD研究新模式。

Berberine is one of the most studied original natural drugs in China in recent years. It is a new lipid-lowering drug with completely different mechanism from statins, which has been used in the multi-center clinical trials. However, berberine is poorly absorbed in the intestinal tract after oral administration leading a significant pharmacokinetic characteristic of low blood concentration（1%） and bioavailability（〈5%）. That is to say, it is difficult to explain the therapeutical effect in vivo by the current pharmacokinetic results. In fact, this phenomenon also exists in a number of clinically effective natural drugs. This review introduces the pharmacokinetic characteristic of berberine by focusing on the gut microbiota to mediate the metabolic process of berberine in vivo. Meanwhile, taking berberine as an example, we emphasized the important role of intestinal bacteria on the pharmacokinetic study on the oral chemical drugs, and put forward a new research mode of drug PK-PD mediated by the gut microbiota.