Evaluation of drug-drug interaction in the hepatobiliary and renal transport of drugs

Annu Rev Pharmacol Toxicol. 2005;45:689-723. doi: 10.1146/annurev.pharmtox.44.101802.121444.

Abstract

Recent studies have revealed the import role played by transporters in the renal and hepatobiliary excretion of many drugs. These transporters exhibit a broad substrate specificity with a degree of overlap, suggesting the possibility of transporter-mediated drug-drug interactions with other substrates. This review is an overview of the roles of transporters and the possibility of transporter-mediated drug-drug interactions. Among the large number of transporters, we compare the Ki values of inhibitors for organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) and their therapeutic unbound concentrations. Among them, cephalosporins and probenecid have the potential to produce clinically relevant OAT-mediated drug-drug interactions, whereas cyclosporin A and rifampicin may trigger OATP-mediated ones. These drugs have been reported to cause drug-drug interactions in vivo with OATs or OATP substrates, suggesting the possibility of transporter-mediated drug-drug interactions. To avoid adverse consequences of such transporter-mediated drug-drug interactions, we need to be more aware of the role played by drug transporters as well as those caused by drug metabolizing enzymes.

Publication types

  • Review

MeSH terms

  • Animals
  • Biliary Tract / drug effects
  • Biliary Tract / metabolism*
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Drug Evaluation / methods
  • Drug Interactions / physiology
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism*
  • Liver / drug effects
  • Liver / metabolism*
  • Pharmaceutical Preparations / metabolism*

Substances

  • Pharmaceutical Preparations