EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS

Shitara, Yoshihisa; Sato, Hitoshi; Sugiyama, Yuichi

doi:10.1146/annurev.pharmtox.44.101802.121444

Cited by 337Drug Transport and Resistance MechanismsPharmacogenetics and Drug MetabolismProtein Interaction Studies and Fluorescence Analysis

EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS

Shitara, Yoshihisa, Sato, Hitoshi, Sugiyama, Yuichi·2005·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev.pharmtox.44.101802.121444

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Abstract

Recent studies have revealed the import role played by transporters in the renal and hepatobiliary excretion of many drugs. These transporters exhibit a broad substrate specificity with a degree of overlap, suggesting the possibility of transporter-mediated drug-drug interactions with other substrates. This review is an overview of the roles of transporters and the possibility of transporter-mediated drug-drug interactions. Among the large number of transporters, we compare the Ki values of inhibitors for organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) and their therapeutic unbound concentrations. Among them, cephalosporins and probenecid have the potential to produce clinically relevant OAT-mediated drug-drug interactions, whereas cyclosporin A and rifampicin may trigger OATP-mediated ones. These drugs have been reported to cause drug-drug interactions in vivo with OATs or OATP substrates, suggesting the possibility of transporter-mediated drug-drug interactions. To avoid adverse consequences of such transporter-mediated drug-drug interactions, we need to be more aware of the role played by drug transporters as well as those caused by drug metabolizing enzymes.

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In the disposition process, transporters and enzymes play a key role by interacting with each other.
“In the disposition process, transporters and enzymes play a key role by interacting with each other [86].”
From Interpretation of Non-Clinical Data for Prediction of Human Pharmacokinetic Parameters: In Vitro-In Vivo Extrapolation and Allometric Scaling (2019) · cites this paper as [86]

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Membrane transporters in drug development
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Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?
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Effects of Drug Transporters on Volume of Distribution
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Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity
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Authors: Shitara, Y., Sato, H., & Sugiyama, Y.
Affiliations: SHOWA Medical University (JP)
The University of Tokyo (JP)
ORCID: Sato, Hitoshi
Sugiyama, Yuichi
Venue: Annual Review of Pharmacology and Toxicology
Publisher: Annual Reviews
Published: 2005-09-22
Volume: 45
Issue: 1
Pages: 689-723
ISSN: 0362-1642 (ISSN-L)
1545-4304
DOI: 10.1146/annurev.pharmtox.44.101802.121444
OpenAlex: W2066382275
Cited by: 336
References: 199
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 14 · 2016: 15 · 2015: 12 · 2014: 14 · 2013: 23 · 2012: 25
FWCI: 2.12
Type: journal article
Language: en
Open access: closed
Locations: The Annual Review of Pharmacology and Toxicology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
Keywords: drug-drug interactions, drug transporters, renal drug excretion, organic anion transporting polypeptides, organic anion transporters, transporter inhibitors, Ki values, substrate specificity, probenecid, cephalosporins, cyclosporine, rifampicin, drug-metabolizing enzymes
MeSH terms: Animals, Biliary Tract, Biological Transport, Drug Evaluation, Drug Interactions, Pharmaceutical Preparations, Humans, Kidney, Liver

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EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS

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