The DOI matches its Crossref record; 127 of the 127 references it cites were found in a registry or an index.
Species differences in drug transporters and implications for translating preclinical findings to humans
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.
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Cites
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Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment
Jang, K.-J., Mehr, A. P., Hamilton, G. A., McPartlin, L. A., Chung, S., Suh, K.-Y., & Ingber, D. E. (2013) · Integrative Biology · doi:10.1039/c3ib40049b · Cited by 849
Raub, T. J., Wishart, G. N., Kulanthaivel, P., Staton, B. A., Ajamie, R. T., Sawada, G. A., Gelbert, L. M., Shannon, H. E., Sanchez-Martinez, C., & De Dios, A. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.114.062745 · Cited by 284
Organs-on-a-chip: a new tool for drug discovery
Polini, A., Prodanov, L., Bhise, N. S., Manoharan, V., Dokmeci, M. R., & Khademhosseini, A. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.886562 · Cited by 223
Cardiovascular organ-on-a-chip platforms for drug discovery and development
Ribas, J., Sadeghi, H., Manbachi, A., Leijten, J., Brinegar, K., Zhang, Y. S., Ferreira, L., & Khademhosseini, A. (2016) · Applied In Vitro Toxicology · doi:10.1089/aivt.2016.0002 · Cited by 161
Mathialagan, S., Piotrowski, M. A., Tess, D. A., Feng, B., Litchfield, J., & Varma, M. V. (2017) · Drug Metabolism and Disposition · doi:10.1124/dmd.116.074294 · Cited by 128
Metadata
- Authors
- Chu, X., Bleasby, K., & Evers, R.
- Venue
- Expert Opinion on Drug Metabolism & Toxicology
- Publisher
- Informa UK Limited
- Published
- 2012-12-21
- Volume
- 9
- Issue
- 3
- Pages
- 237-252
- ISSN
- 1742-5255 (ISSN-L)
- 1744-7607
- OpenAlex
- W2110057699
- Cited by
- 306
- References
- 127
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- closed
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