title: Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.
abstract: The study investigated whether quinolone antibiotics inhibit the PEPT1-mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine-Ψ(CN-S)-alanine (Phe-Ψ-Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (C(max)) of orally administered Phe-Ψ-Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration-time curve (AUC) of orally administered Phe-Ψ-Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe-Ψ-Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug-drug interaction.
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arakawa
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kamioka
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kanagawa
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hatano
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Idota
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yano
authors.affiliation: Department of Drug Absorption and Pharmacokinetics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai, Miyagi, 981-8558, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Morimoto
authors.affiliation: Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi Takasaki-shi, Gunma, 370-0033, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004347:Drug Interactions; D006367:HeLa Cells; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D000074011:Peptide Transporter 1; D010455:Peptides / Q000493:pharmacokinetics; D010649:Phenylalanine / Q000097:blood / Q000493:pharmacokinetics*; D015363:Quinolones / Q000494:pharmacology*; D017208:Rats, Wistar; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000074011:Peptide Transporter 1; D010455:Peptides; D015363:Quinolones; C082186:SLC15A1 protein, human; D027981:Symporters; D010649:Phenylalanine
keywords: absorption; interaction; peptide transporter 1; quinolone antibiotics; transporter