Hepatobiliary transporters in the pharmacology and toxicology of anticancer drugs.
The existence of carrier proteins located in the basolateral and apical membranes of hepatocytes, cholangiocytes and epithelial cells of the ileal mucosa, together with their more or less broad substrate specificities -implying their ability to transport many different drugs, including anticancer drugs- has important pharmacological repercussions. These vary from the existence of interactions of drugs with endogenous and xenobiotic substances to the possibility of using these transporters in the targeting of drug delivery systems, which can be useful either to direct anticancer drugs towards tumors located in the hepatobiliary system or to facilitate their hepatobiliary excretion. This justifies the growing interest in bile acid derivatives as targeted pharmacological tools, in general, and in anticancer chemotherapy, in particular. Moreover, interactions of antitumor drugs with hepatobiliary transporters may account for the appearance of toxic side effects associated with the use of these drugs. The present review covers these aspects of the pharmacology and toxicology of hepatobiliary transport systems in relation to anticancer drugs.
Marin
Jose J G
JJ
Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), University of Salamanca, CIBERehd, Spain. jjgmarin@usal.es
Briz
Oscar
O
Perez
Maria J
MJ
Romero
Marta R
MR
Monte
Maria J
MJ
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D001659:Biliary Tract / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D002352:Carrier Proteins