ABCB1, ABCG2, ABCC1, ABCC2, and ABCC3 drug transporter polymorphisms and their impact on drug bioavailability: what is our current understanding?

Introduction: Interindividual differences in drug response are a frequent clinical challenge partly due to variation in pharmacokinetics. ATP-binding cassette (ABC) transporters are crucial determinants of drug disposition. They are subject of gene regulation and drug-interaction; however, it is still under debate to which extend genetic variants in these transporters contribute to interindividual variability of a wide range of drugs.

Areas covered: This review discusses the current literature on the impact of genetic variants in ABCB1, ABCG2 as well as ABCC1, ABCC2, and ABCC3 on pharmacokinetics and drug response. The aim was to evaluate if results from recent studies would increase the evidence for potential clinically relevant pharmacogenetic effects.

Expert opinion: Although enormous efforts have been made to investigate effects of ABC transporter genotypes on drug pharmacokinetics and response, the majority of studies showed only weak if any associations. Despite few unique results, studies mostly failed to confirm earlier findings or still remained inconsistent. The impact of genetic variants on drug bioavailability is only minor and other factors regulating the transporter expression and function seem to be more critical. In our opinion, the findings on the so far investigated genetic variants in ABC efflux transporters are not suitable as predictive biomarkers.