High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care

作     者：Jian Li Olajide E.Olaleye Xuan Yu Weiwei Jia Junling Yang Chuang Lu Songqiao Liu Jingjing Yu Xiaona Duan Yaya Wanga Kai Dong Rongrong He Chen Cheng Chuan Li Jian Li;Olajide E.Olaleye;Xuan Yu;Weiwei Jia;Junling Yang;Chuang Lu;Songqiao Liu;Jingjing Yu;Xiaona Duan;Yaya Wang;Kai Dong;Rongrong He;Chen Cheng;Chuan Li

作者机构：State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences University of Chinese Academy of Sciences Department of DMPK Department of Critical Care MedicineZhongda HospitalSchool of MedicineSoutheast University School of PharmacyUniversity of Washington Tianjin Chasesun Pharmaceutical Co.Ltd. 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2019年第9卷第5期

页      面：1035-1049页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100706[医学-药理学] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：funded by grants from the National Science&Technology Major Project of China “Key New Drug Creation and Manufacturing Program”(2017ZX09301012006) the National Basic Research Program of China(2012CB518403) the National Natural Science Foundation of China(81503345) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12050306) 

主　　题：XueBiJing Antibiotic Combination drug therapy Sepsis Pharmacokinetic compatibility Herb-drug interaction 

摘      要：Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding Xue Bi Jing, a five-herb medicine, to antibioticbased sepsis care. Although adding Xue Bi Jing further reduced 28-day mortality via modulating the host response, pharmacokinetic herbedrug interaction is a widely recognized issue that needs to be *** on our earlier systematic chemical and human pharmacokinetic investigations of Xue Bi Jing, we evaluated the degree of pharmacokinetic compatibility for Xue Bi Jing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both Xue Bi Jing-antibiotic and antibiotic-Xue Bi Jing 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 Xue Bi Jing 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 Xue Bi Jing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could,due to their inhibition of uridine 50-diphosphoglucuronosyltransferase 2 B15, organic anion transporters1/2 and/or organic anion-transporting polypeptide 1 B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions(resulting in increased exposure) are likely desirable due to these Xue Bi Jing compounds’ low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from Xue Bi ***, Xue Bi Jing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.