Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Incorporating other mechanisms (reactive metabolite and cytotoxic metabolite generation and hepatic efflux transport inhibition, other than BSEP) to the HRM had minimal beneficial impact in DILI prediction/stratification.
|
31532188 |
2020 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
We present a quantitative and mechanistic risk assessment for candidate nomination using data from <i>in vitro</i> assays (hepatic spheroids, BSEP, mitochondrial toxicity, and bioactivation), together with physicochemical (cLogP) and exposure (Cmax<sub>total</sub>) variables from a chemically diverse compound set (33 no/low-, 40 medium-, and 23 high-severity DILI compounds).
|
31535850 |
2020 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
In conclusion, differential inhibition of TCA or GCA transport cannot account for an association between the variant BSEP and the risk for cholestatic DILI due to the drugs tested.
|
30608704 |
2019 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
A potent BSEP inhibitor, ketoconazole (KTZ), which is associated with clinical DILI, was intragastrically administered simultaneously with CDCA at a nontoxic dose once a day for 3 days.
|
30985903 |
2019 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
The C-DILI™ assay integrates the effects of bile salt export pump inhibition, farnesoid X receptor antagonism, and basolateral efflux inhibition of bile acids to more accurately predict a drug's potential to cause cholestatic hepatotoxicity and drug-induced liver injury.
|
31016648 |
2019 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Inhibition of the bile salt export pump (BSEP) may be associated with clinical drug-induced liver injury, but is poorly predicted by preclinical animal models.
|
30903168 |
2019 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
One compound known for potent BSEP inhibition and severe DILI is troglitazone.
|
29146462 |
2018 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Since BDDCS class is not related to any proposed DILI mechanistic hypotheses, we maintain that if measures of BSEP inhibition alone or together with inhibition of other transporters cannot be differentiated from class 2 assignment, there is no support for in vitro BSEP inhibition being DILI predictive.
|
29272540 |
2018 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
BSEP inhibition is one of several mechanisms by which drugs may cause DILI, therefore, it should be considered alongside other mechanisms when evaluating possible DILI risk.
|
30137645 |
2018 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
In vitro inhibition of the bile salt export pump (BSEP) has become a major risk factor for in vivo DILI predictions, yet discrepancies exist in which methods to use and the extent to which BSEP inhibition predicts clinical DILI.
|
28369588 |
2017 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
In the present study, we employ two in silico methods, random forest (RF) and the pharmacophore method, to recognize potential BSEP inhibitors that could cause cholestatic DILI, with the aim of mitigating the risk of cholestatic DILI to some extent.
|
28092392 |
2017 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
To better understand the numerous mechanisms of DILI, recent efforts have focused on transporter inhibition, specifically liver canalicular bile salt export pump (Bsep) as one mechanism of DILI, and on the potential use of plasma bile acids as monitorable mechanism-based biomarkers of Bsep inhibition.
|
28108666 |
2017 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
Role of polymorphic bile salt export pump (BSEP, ABCB11) transporters in anti-tuberculosis drug-induced liver injury in a Chinese cohort.
|
27293027 |
2016 |
Drug-Induced Liver Disease
|
0.100 |
Biomarker
|
phenotype |
BEFREE |
As intracellular BA accumulation is determined by BSEP function and the subsequent adaptive gene regulation, assessment of intracellular BA accumulation in HepaRG-KO cells could be a useful approach to evaluate drug-induced liver injury (DILI) potentials of drugs that could disrupt other BA homeostasis pathways beyond BSEP inhibition.
|
26910619 |
2016 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
On sequencing, ATP8B1 was normal in both patients although the younger was heterozygous for the c.2093G>A mutation in ABCB11, a polymorphism previously encountered in drug-induced liver injury.
|
23750872 |
2013 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Patients carrying the C allele in the ABCB11 1331T>C polymorphism are at increased risk of developing hepatocellular type of DILI, when taking drugs containing a carbocyclic system with aromatic rings.
|
23701583 |
2013 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Twelve functional polymorphisms in five genes (ABCB11, ABCC2, CYP2C9, SLCO1B1, and SLCO1B3) implicated in bosentan pharmacokinetics were tested for associations with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and DILI.
|
23863877 |
2013 |
Drug-Induced Liver Disease
|
0.100 |
GeneticVariation
|
phenotype |
BEFREE |
Four highly conserved nonsynonymous mutations were specific for drug-induced liver injury [ABCB11: D676Y (drug-induced cholestasis) and G855R (drug-induced cholestasis); ABCB4: I764L (drug-induced cholestasis) and L1082Q (drug-induced hepatocellular injury)].
|
17264802 |
2007 |