The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Protein Abundance of Clinically Relevant Multidrug Transporters along the Entire Length of the Human Intestine
Abstract
Intestinal transporters are crucial determinants in the oral absorption of many drugs. We therefore studied the mRNA expression (N = 33) and absolute protein content (N = 10) of clinically relevant transporters in healthy epithelium of the duodenum, the proximal and distal jejunum and ileum, and the ascending, transversal, descending, and sigmoidal colon of six organ donors (24-54 years). In the small intestine, the abundance of nearly all studied proteins ranged between 0.2 and 1.6 pmol/mg with the exception of those of OCT3 (<0.1 pmol/mg) and PEPT1 (2.6-4.9 pmol/mg) that accounted for ∼50% of all measured transporters. OATP1A2 was not detected in any intestinal segment. ABCB1, ABCG2, PEPT1, and ASBT were significantly more abundant in jejunum and ileum than in colon. In contrast to this, the level of expression of ABCC2, ABCC3, and OCT3 was found to be highest in colon. Site-dependent differences in the levels of gene and protein expression were observed for ABCB1 and ASBT. Significant correlations between mRNA and protein levels have been found for ABCG2, ASBT, OCT3, and PEPT1 in the small intestine. Our data provide further physiological pieces of the puzzle required to predict intestinal drug absorption in humans.
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Cites
Arzneimittelforschung: Erstanwendung am Menschen in der Phase I
Miletzki, B., & Gleiter, C. H. (2005) · Bundesgesundheitsblatt Gesundheitsforsch.Gesundheitsschutz · doi:10.1007/s00103-005-1024-7 · Cited by 9,355
Membrane transporters in drug development
The International Transporter Consortium, Giacomini, K. M., Huang, S.-M., Tweedie, D. J., Benet, L. Z., Brouwer, K. L. R., Chu, X., Dahlin, A., Evers, R., Fischer, V., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3028 · Cited by 3,340
A "Silent" Polymorphism in the MDR 1 Gene Changes Substrate Specificity
Kimchi-Sarfaty, C., Oh, J. M., Kim, I.-W., Sauna, Z. E., Calcagno, A. M., Ambudkar, S. V., & Gottesman, M. M. (2007) · Science · doi:10.1126/science.1135308 · Cited by 2,416
Measurement of gastrointestinal pH profiles in normal ambulant human subjects
Evans, D. F., Pye, G., Bramley, R., Clark, A. G., Dyson, T. J., & Hardcastle, J. D. (1988) · Gut · doi:10.1136/gut.29.8.1035 · Cited by 1,240
Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors
Uchida, Y., Ohtsuki, S., Katsukura, Y., Ikeda, C., Suzuki, T., Kamiie, J., & Terasaki, T. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07208.x · Cited by 881
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Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging
SCHILLER, C., FRÖHLICH, C. ‐., GIESSMANN, T., SIEGMUND, W., MÖNNIKES, H., HOSTEN, N., & WEITSCHIES, W. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02683.x · Cited by 596
Self-citationHilgendorf, C., Ahlin, G., Seithel, A., Artursson, P., Ungell, A.-L., & Karlsson, J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.014902 · Cited by 583
Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects
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Cited by
Verma, S., Goand, U. K., Husain, A., Katekar, R. A., Garg, R., & Gayen, J. R. (2021) · Drug Development Research · doi:10.1002/ddr.21832 · Cited by 151
Killer, M., Wald, J., Pieprzyk, J., Marlovits, T. C., & Löw, C. (2021) · Science Advances · doi:10.1126/sciadv.abk3259 · Cited by 94
Li, C. Y., Basit, A., Gupta, A., Gáborik, Z., Kis, E., & Prasad, B. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.03.027 · Cited by 73
Self-citationBoosting drug bioavailability in men but not women through the action of an excipient
Mai, Y., Ashiru-Oredope, D. A. I., Yao, Z., Dou, L., Madla, C. M., Taherali, F., Murdan, S., & Basit, A. W. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119678 · Cited by 28
Metadata
- Authors
- Drozdzik, M., Gröer, C., Penski, J., Lapczuk, J., Ostrowski, M., Lai, Y., Prasad, B., Unadkat, J. D., Siegmund, W., & Oswald, S.
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-09-11
- Volume
- 11
- Issue
- 10
- Pages
- 3547-3555
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2324292926
- Cited by
- 258
- References
- 49
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- closed
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