Pharmacogenetics of Drug Transporters in the Enterohepatic Circulation

Abstract

This article summarizes the impact of the pharmacogenetics of drug transporters expressed in the enterohepatic circulation on the pharmacokinetics and pharmacodynamics of drugs. The role of pharmacogenetics in the function of drug transporter proteins in vitro is now well established and evidence is rapidly accumulating from in vivo pharmacokinetic studies, which suggests that genetic variants of drug transporter proteins can translate into clinically relevant phenotypes. However, a large amount of conflicting information on the clinical relevance of drug transporter proteins has so far precluded the emergence of a clear picture regarding the role of drug transporter pharmacogenetics in medical practice. This is very well exemplified by the case of P-glycoprotein (MDR1, ABCB1). The challenge is now to develop pharmacogenetic models with sufficient predictive power to allow for translation into drug therapy. This will require a combination of pharmacogenetics of drug transporters, drug metabolism and pharmacodynamics of the respective drugs.

KEYWORDS::

• adverse drug events
• drug disposition
• enterohepatic circulation
• intestine
• liver
• pharmacokinetics

Acknowledgements

The authors thank Sarah Steinbacher, scientific illustrator at Multimedia and E-learning Services, University of Zurich, Switzerland, for the design of Figure 1.

Financial & competing interests disclosure

Bruno Stieger is supported by grant #31003A_124652 from the Swiss National Science Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Bruno Stieger is supported by grant #31003A_124652 from the Swiss National Science Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.