Journal
PHARMACOGENOMICS
Volume 12, Issue 5, Pages 611-631Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.11.53
Keywords
adverse drug events; drug disposition; enterohepatic circulation; intestine; liver; pharmacokinetics
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Funding
- Swiss National Science Foundation [31003A_124652]
- Swiss National Science Foundation (SNF) [31003A_124652] Funding Source: Swiss National Science Foundation (SNF)
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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.
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