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Current Concepts in Drug-Induced Bile Salt Export Pump (BSEP) Interference
1Safety Science Consultant, Macclesfield, Cheshire, United Kingdom.
Current Protocols in Toxicology
|August 9, 2014
Summary
Drug inhibition of the Bile Salt Export Pump (BSEP) can cause liver injury. Evaluating BSEP inhibition is crucial for drug development to mitigate risks of drug-induced liver injury (DILI).
Area of Science:
- Hepatology
- Pharmacology
- Drug Metabolism
Background:
- Drug-induced liver injury (DILI) is a significant safety concern.
- Inhibition of the Bile Salt Export Pump (BSEP) is a known mechanism contributing to DILI.
- Regulatory agencies and industry recognize the importance of assessing BSEP inhibition.
Purpose of the Study:
- To discuss methods for assessing BSEP inhibition.
- To highlight the role of BSEP inhibition in DILI.
- To identify knowledge gaps in understanding BSEP's role in DILI.
Main Methods:
- Review of existing literature on BSEP inhibition assays.
- Analysis of regulatory guidelines and industry recommendations.
- Discussion of nonclinical and clinical study findings related to BSEP and DILI.
Main Results:
- Various methods exist to assess and quantify BSEP inhibition.
- BSEP inhibition is a recognized risk factor for cholestatic DILI.
- Current understanding of the BSEP-DILI relationship has key limitations.
Conclusions:
- Assessing BSEP inhibition is vital during drug development to predict and prevent DILI.
- Further research is needed to fully elucidate the mechanisms linking BSEP inhibition to DILI.
- Minimizing BSEP inhibition early in drug discovery can reduce DILI risk.
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