{"id":2908,"date":"2026-08-22T15:49:03","date_gmt":"2026-08-22T14:49:03","guid":{"rendered":"https:\/\/seamlessbio.de\/?page_id=2908"},"modified":"2026-08-23T00:56:25","modified_gmt":"2026-08-22T23:56:25","slug":"what-is-bsep","status":"publish","type":"page","link":"https:\/\/seamlessbio.de\/de\/what-is-bsep\/","title":{"rendered":"What is BSEP"},"content":{"rendered":"
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Quick Definition<\/p>\n

What is BSEP (Bile Salt Export Pump)?:<\/strong> BSEP (Bile Salt Export Pump, ABCB11) is an ABC efflux transporter located on the canalicular membrane of hepatocytes. It is the primary transporter responsible for secreting bile salts from hepatocytes into bile. Inhibition of BSEP by drugs causes intracellular bile salt accumulation, leading to hepatocellular injury \u2014 a major mechanism of drug-induced liver injury (DILI).<\/p>\n<\/div>\n\n

Why does BSEP inhibition cause liver injury?<\/h2>\n

Bile salts are produced in hepatocytes and must be actively pumped into bile by BSEP to prevent toxic accumulation. When BSEP is inhibited by a drug, bile salts accumulate inside hepatocytes to concentrations that cause direct membrane damage, mitochondrial dysfunction, and activation of apoptotic pathways. This manifests clinically as cholestatic hepatitis \u2014 elevated alkaline phosphatase, conjugated bilirubin, and GGT, with or without elevated transaminases.<\/p>\n\n

How is BSEP inhibition tested?<\/h2>\n

BSEP inhibition is assessed using the vesicular transport assay with inside-out membrane vesicles prepared from cells overexpressing human BSEP (ABCB11). The probe substrate is taurocholic acid (TCA). The test compound is incubated at multiple concentrations alongside TCA and ATP \u2014 the reduction in ATP-dependent TCA accumulation gives the IC50. An IC50 below the estimated unbound hepatic concentration triggers a DILI risk flag requiring further investigation.<\/p>\n\n

Zulassungsstatus<\/h2>\n

FDA's 2020 DDI guidance does not explicitly mandate BSEP testing. ICH M12 (2022), EMA DDI guideline, and PMDA all recommend BSEP inhibition assessment for drugs with hepatic involvement. Omitting BSEP from an IND package for a hepatically-eliminated drug routinely generates regulatory questions.<\/p>\n\n

Key Facts<\/h2>\n