5,388
Views
228
CrossRef citations to date
0
Altmetric
Reviews

Species differences in drug transporters and implications for translating preclinical findings to humans

, &
Pages 237-252 | Published online: 21 Dec 2012
 

Abstract

Introduction: Drug transporters play an important role in the absorption, distribution, and excretion (ADE) of many drugs. In the last several years it has become increasingly clear that there are significant differences between rodents, dog, monkey, and human in the substrate specificity, tissue distribution, and relative abundance of transporters. These differences complicate cross-species extrapolations, which is important when attempting to predict human pharmacokinetics (PK) of drug candidates and assess risk for drug–drug interactions (DDIs).

Areas covered: This article provides an overview of species differences for the major transporters involved in drug disposition. Specifically, the article looks at a number of efflux and uptake transporters including multidrug resistance protein MDR1 P-glycoprotein (Pgp), breast cancer resistance protein (BCRP), multidrug resistance proteins (MRPs), members of the multidrug resistance and toxic extrusion protein (MATE) family, as well as members of organic anion transporting polypeptides (OATPs), organic anion transporters (OATs), and organic cation transporters (OCTs).

Expert opinion: Quantitative knowledge of species differences of transporters, especially at the protein and functional level is still limited. The current challenge is to extrapolate and integrate data from both preclinical species and humans to quantitatively predict the impact of transporters on drug absorption, disposition, and drug–drug interactions. Increased understanding of species differences in transporter expression and functional activity is needed in order to translate findings from preclinical species to humans. Ultimately, high quality in vitro and in vivo data will aid in the establishment of physiologically based pharmacokinetic (PBPK) models, which will improve the capability to predict PK characteristics of drug candidates in humans.

Acknowledgements

We thank J Hochman and T Nguyen for critically reading the manuscript and valuable comments.

Declaration of interest

The authors are all employees of Merck & Co., Inc. and may hold stock or stock options in the company.

Notes

This box summarizes key points contained in the article.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 99.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 727.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.