Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective.
Clin Pharmacol Ther
; 104(5): 916-932, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-30137645
ABSTRACT
Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug-induced liver injury (DILI). Proactive evaluation and understanding of BSEP inhibition is recommended in drug discovery and development to aid internal decision making on DILI risk. BSEP inhibition can be quantified using in vitro assays. When interpreting assay data, it is important to consider in vivo drug exposure. Currently, this can be undertaken most effectively by consideration of total plasma steady state drug concentrations (Css,plasma ). However, because total drug concentrations are not predictive of pharmacological effect, the relationship between total exposure and BSEP inhibition is not causal. Various follow-up studies can aid interpretation of in vitro BSEP inhibition data and may be undertaken on a case-by-case basis. 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bile
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Moduladores de Transporte de Membrana
/
Descoberta de Drogas
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Doença Hepática Induzida por Substâncias e Drogas
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Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
/
Desenvolvimento de Medicamentos
/
Fígado
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Reino Unido