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首页> 美国卫生研究院文献>Acta Pharmaceutica Sinica. B >High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care
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High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care

机译：五药血必净与败血症护理中使用的抗生素之间存在高度的药代动力学相容性

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摘要

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality via modulating the host response, pharmacokinetic herb–drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5′-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.
机译：处理败血症宿主对感染的反应失调仍然是一项重大挑战。中医治疗指南建议在以抗生素为基础的败血症治疗中加用五药学血净。尽管添加血必净通过调节宿主反应进一步降低了28天的死亡率，但药代动力学药-药相互作用是一个广泛研究的问题，需要研究。基于我们对血必净的较早的系统化学和人类药代动力学研究，我们基于相互作用风险的机械证据评估了血必净/抗生素组合的药代动力学相容性程度。考虑到血必净与抗生素的相互作用潜力，我们将基于信息学的方法与实验方法相结合，并开发了基于复合对的数据处理方法。为了反映临床现实，我们选择了可用于药物相互作用的可生物利用的血必净化合物和中国败血症护理中常用的45种抗生素进行研究。根据与药物代谢酶和转运蛋白相互作用的数据，作为致病剂的血必净化合物不能与抗生素配对。尽管某些抗生素可以抑制尿苷5'-二磷酸葡萄糖醛酸糖基转移酶2B15，但有机阴离子转运蛋白1/2和/或有机阴离子转运多肽1B3与senkyunolide I，丹参醇和丹酚酸B配对，但潜在的相互作用（导致由于这些血必净化合物的基线暴露水平较低，因此可能需要增加暴露水平。 7种抗生素对醛脱氢酶的抑制作用可能会导致不良的减少血必净对原儿茶酸的暴露。总体而言，血必净/抗生素组合在临床相关剂量下显示出高度的药代动力学相容性。开发的方法可用于研究其他药物组合。

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