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Titolo:
CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs
Autore:
Han, HK; Rhie, JK; Oh, DM; Saito, G; Hsu, CP; Stewart, BH; Amidon, GL;
Indirizzi:
Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Coll Pharm, Ann Arbor, MI 48109 USA WarnergLambert Parke Davis, Parke Davis Pharmaceut Res, Pharmacokinet & Dru Warner Lambert Parke Davis Ann Arbor MI USA 48105 es, Pharmacokinet & Dru
Titolo Testata:
JOURNAL OF PHARMACEUTICAL SCIENCES
fascicolo: 3, volume: 88, anno: 1999,
pagine: 347 - 350
SICI:
0022-3549(199903)88:3<347:CCOTHP>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-LACTAM ANTIBIOTICS; MEMBRANE ABSORPTION PARAMETERS; RAT INTESTINE INSITU; HAMSTER OVARY CELLS; DIPEPTIDE TRANSPORTER; ORAL ABSORPTION; CACO-2 CELLS; SYSTEM; CARRIER; PERMEABILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Amidon, GL Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA Univ Michigan 428 Church St Ann Arbor MI USA 48109 MI 48109 USA
Citazione:
H.K. Han et al., "CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs", J PHARM SCI, 88(3), 1999, pp. 347-350

Abstract

The present study characterized Chinese hamster ovary cells overexpressinga 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 beta-lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO-Kf cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugsalso 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 beta-lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, L-dopa and alpha-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.

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Documento generato il 06/07/20 alle ore 08:43:14