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Cited by 418

The DOI matches its Crossref record; 151 of the 151 references it cites were found in a registry or an index.

Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption

Shitara, Yoshihisa, Maeda, Kazuya, Ikejiri, Kazuaki, Yoshida, Kenta, Horie, Toshiharu, Sugiyama, Yuichi·2013·Biopharmaceutics & Drug Disposition
DOI 10.1002/bdd.1823
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Abstract

Organic anion transporting polypeptide (OATP) family transporters accept a number of drugs and are increasingly being recognized as important factors in governing drug and metabolite pharmacokinetics. OATP1B1 and OATP1B3 play an important role in hepatic drug uptake while OATP2B1 and OATP1A2 might be key players in intestinal absorption and transport across blood–brain barrier of drugs, respectively. To understand the importance of OATPs in the hepatic clearance of drugs, the rate‐determining process for elimination should be considered; for some drugs, hepatic uptake clearance rather than metabolic intrinsic clearance is the more important determinant of hepatic clearances. The importance of the unbound concentration ratio (liver/blood),Kp,uu, of drugs, which is partly governed by OATPs, is exemplified in interpreting the difference in the IC 50 of statins between the hepatocyte and microsome systems for the inhibition of HMG‐CoA reductase activity. The intrinsic activity and/or expression level of OATPs are affected by genetic polymorphisms and drug–drug interactions. Their effects on the elimination rate or intestinal absorption rate of drugs may sometimes depend on the substrate drug. This is partly because of the different contribution of OATP isoforms to clearance or intestinal absorption. When the contribution of the OATP‐mediated pathway is substantial, the pharmacokinetics of substrate drugs should be greatly affected. This review describes the estimation of the contribution of OATP1B1 to the total hepatic uptake of drugs from the data of fold‐increases in the plasma concentration of substrate drugs by the genetic polymorphism of this transporter. To understand the importance of the OATP family transporters, modeling and simulation with a physiologically based pharmacokinetic model are helpful. Copyright © 2012 John Wiley & Sons, Ltd.

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Metadata

Authors
Shitara, Y., Maeda, K., Ikejiri, K., Yoshida, K., Horie, T., & Sugiyama, Y.
Venue
Biopharmaceutics & Drug Disposition
Publisher
Wiley
Published
2013-01
Volume
34
Issue
1
Pages
45-78
ISSN
  • 0142-2782 (ISSN-L)
  • 1099-081X
DOI
10.1002/bdd.1823
OpenAlex
W1868407335
Cited by
418
References
151
FWCI
12.78
Type
journal article
Language
en
Open access
closed

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