The role of organic anion transporting polypeptides in drug absorption, distribution, excretion and drug-drug interactions

ABSTRACT

Introduction: The in vivo fate and effectiveness of a drug depends highly on its absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Organic anion transporting polypeptides (OATPs) are membrane proteins involved in the cellular uptake of various organic compounds, including clinically used drugs. Since OATPs are significant players in drug absorption and distribution, modulation of OATP function via pharmacotherapy with OATP substrates/inhibitors, or modulation of their expression, affects drug pharmacokinetics. Given their cancer-specific expression, OATPs may also be considered anticancer drug targets.

Areas covered: We describe the human OATP family, discussing clinically relevant consequences of altered OATP function. We offer a critical analysis of published data on the role of OATPs in ADME and in drug–drug interactions, especially focusing on OATP1A2, 1B1, 1B3 and 2B1.

Expert opinion: Four members of the OATP family, 1A2, 1B1, 1B3 and 2B1, have been characterized in detail. As biochemical and pharmacological knowledge on the other OATPs is lacking, it seems timely to direct research efforts towards developing the experimental framework needed to investigate the transport mechanism and substrate specificity of the poorly described OATPs. In addition, elucidating the role of OATPs in tumor development and therapy response are critical avenues for further research.

KEYWORDS:

• Drug-drug interaction
• hepatic clearance
• intestinal absorption
• organic anion transporting polypeptides
• pharmacokinetics
• pharmacogenetics
• ADME
• GWAS

Article highlights

• OATPs 1A2, 1B1, 1B3 and 2B1 are multi-specific transporters involved in the absorption, distribution and elimination of widely used drugs

• The function of these OATPs can be altered by genetic variations and drug interactions that result in altered pharmacokinetics (PK) and toxicity

• Based on their expression in barrier tissues (blood-brain barrier, placenta) and in detoxifying organs, lesser known members of the OATP family may also influence PK

• Research efforts should be directed at the development of the experimental toolkit needed to elucidate the role of the less described OATPs in ADME

• Increased expression of selected OATPs in cancer may be exploited by novel anti-cancer therapy

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Declaration of interest

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.

Additional information

Funding

This research has been supported by research grants from the Hungarian Scientific Research Fund (OTKA, K 109423) and MedInProt. C Özvegy-Laczka is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences.