Hepatobiliary trans-membranetransport regulates intracellular exposure to xenobiotic and endogenouschemicals and metabolites. The mechanism for liver injury of several withdrawntherapeutics involves abrogation of the bile salt export pump (BSEP) functionand animal results do not correlate well with clinical hepatoxicity.  BSEP impedance by drugs correlates with humanhepatoxicity; in some cases the function of P-glycoprotein and/or BCRP cancompensate for the abrogation of the BSEP transport of xenobiotics. Insufficientrouting of acyl-glucuronides due to ABC-C2 inhibition can result inhepatotoxicity.  In addition to various hepatotoxicantsthat rely on transporters to influence the degree of severity there are manyneurotoxins that are precluded from the CNS/CNF by transporters at theblood-brain barrier. Uptake transporters such as OATPs and OCTs canenrich some xenobiotics to concentrations above the tolerability window. Certain drugs potently inhibit OATP1B1,causing clinically significant drug interactions.

Role and influence of trans-membrane
transporters in toxicity

242nd National Meeting (2011)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Role and influence of trans-membrane transporters in toxicity