CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs
dc.contributor.author | Han, Hyo-kyung | en_US |
dc.contributor.author | Rhie, Julie K. | en_US |
dc.contributor.author | Oh, Doo-man | en_US |
dc.contributor.author | Saito, Go | en_US |
dc.contributor.author | Hsu, Cheng-Pang | en_US |
dc.contributor.author | Stewart, Barbra H. | en_US |
dc.contributor.author | Amidon, Gordon L. | en_US |
dc.date.accessioned | 2006-04-19T13:37:02Z | |
dc.date.available | 2006-04-19T13:37:02Z | |
dc.date.issued | 1999-03 | en_US |
dc.identifier.citation | Han, Hyo-kyung; Rhie, Julie K.; Oh, Doo-man; Saito, Go; Hsu, Cheng-pang; Stewart, Barbra H.; Amidon, Gordon L. (1999)."CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs." Journal of Pharmaceutical Sciences 88(3): 347-350. <http://hdl.handle.net/2027.42/34496> | en_US |
dc.identifier.issn | 0022-3549 | en_US |
dc.identifier.issn | 1520-6017 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34496 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10052994&dopt=citation | en_US |
dc.description.abstract | The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO–K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. V max in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO–K1 cells, while K m values were similar in all cases. The uptake of β -lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO–K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO–K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as β -lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, l -dopa and α -methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter. | en_US |
dc.format.extent | 70131 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | John Wiley & Sons, Inc. | en_US |
dc.subject.other | Chemistry | en_US |
dc.subject.other | Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry | en_US |
dc.title | CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pharmacy and Pharmacology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationum | College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. ; College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065. | en_US |
dc.contributor.affiliationother | Pharmacokinetics and Drug Metabolism Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105. | en_US |
dc.identifier.pmid | 10052994 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34496/1/11_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/(ISSN)1520-6017 | en_US |
dc.identifier.source | Journal of Pharmaceutical Sciences | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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