High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care.
10.1016/j.apsb.2019.06.003
- Author:
Jian LI
1
;
Olajide E OLALEYE
1
;
Xuan YU
1
;
Weiwei JIA
1
;
Junling YANG
1
;
Chuang LU
2
;
Songqiao LIU
3
;
Jingjing YU
4
;
Xiaona DUAN
1
;
Yaya WANG
1
;
Kai DONG
5
;
Rongrong HE
1
;
Chen CHENG
1
;
Chuan LI
1
Author Information
1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
2. Department of DMPK, Sanofi, Waltham, MA 02451, USA.
3. Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
4. School of Pharmacy, University of Washington, Seattle, WA 98105, USA.
5. Tianjin Chasesun Pharmaceutical Co. Ltd., Tianjin 301700, China.
- Publication Type:Journal Article
- Keywords:
4-MU, 4-methylumbelliferone;
4-MUG, 4-methylumbelliferyl-β-d-glucuronide;
ABC transporter, ATP-binding cassette transporter;
ADR, adverse drug reaction;
ALDH, aldehyde dehydrogenase;
AMP, adenosine monophosphate;
AQ, amodiaquine;
ATP, adenosine triphosphate;
Antibiotic;
BCRP, breast cancer resistance protein;
BSEP, bile salt export pump;
CLR, renal clearance;
CLtot,p, total plasma clearance;
COMT, catechol-O-methyltransferase;
Cmax, maximum plasma concentration;
Combination drug therapy;
DDI, drug‒drug interaction;
DEAQ, desethylamodiaquine;
E2, β-estradiol;
E217βG, estradiol-17β-d-glucuronide;
E23βG, β-estradiol-3-β-d-glucuronide;
GF, glomerular filtration;
GFR, glomerular filtration rate;
HEK-293, human embryonic kidney 293 cell line;
Herb‒drug interaction;
IC50, half-maximal inhibitory concentration;
Km, Michaelis constant;
MATE, multidrug and toxin extrusion protein;
MDR1, multidrug resistance transporter 1;
MRP, multidrug resistance protein;
NAD+, nicotinamide adenine dinucleotide;
OAT, organic anion transporter;
OATP, organic anion-transporting polypeptide;
OCT, organic cation transporter;
PAH, para-aminohippuric acid;
PK, pharmacokinetic;
PKC, pharmacokinetic compatibility;
Pharmacokinetic compatibility;
SLC transporter, solute carrier transporter;
Sepsis;
TEA, tetraethylammonium;
TFP, trifluoperazine;
TFPG, trifluoperazine-N-β-d-glucuronide;
TS, tubular secretion;
UGT, uridine 5′-diphosphoglucuronosyltransferases;
VSS, apparent volume of distribution at steady state;
XueBiJing;
fe-U, fraction of dose excreted unchanged into urine;
fu-p, unbound fraction in plasma;
t1/2, elimination half-life
- From:
Acta Pharmaceutica Sinica B
2019;9(5):1035-1049
- CountryChina
- Language:English
-
Abstract:
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 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.
