title: Effect of Different Metal Ions on the Biological Properties of Cefadroxil.
abstract: The effect of different metal ions on the intestinal transport and the antibacterial activity of cefadroxil [(6R,7R)-7-{[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid] was investigated. The [14C]Gly-Sar uptake via PEPT1 was inhibited by Zn2+and Cu2+treatment in a concentration-dependent manner (Kivalues 107 ± 23 and 19 ± 5 μM, respectively). Kinetic analysis showed that the Ktof Gly-Sar uptake was increased 2-fold in the presence of zinc sulphate (150 μM) whereas the Vmaxvalue were not affected suggesting that zinc ions inhibited Gly-Sar uptake by PEPT1 in a competitively manner. Ni2+exhibited moderate inhibitory effect, whereas Co2+, Mg2+, Al3+ions showed no inhibitory effect on Gly-Sar uptake via PEPT1. Subsequently, we examined the effect of Zn2+and Al3+ions on the transepithelial transport of cefadroxil across Caco-2 cells cultured on permeable supports. The results showed that zinc ions inhibited the transepithelial flux of cefadroxil at Caco-2 cell monolayers while Al3+ions had no effect. The interaction of cephalosporins with the metal ions could suggest negative effects of some metal ions on the clinical aspects of small intestinal peptide and drug transport. Finally, the effect of Zn2+, Cu2+and Al3+ions on the antibacterial activity of cefadroxil was tested. It was found that there is no significant difference between the activity of cefadroxil and the cefadroxil metal ion complexes studied against the investigated sensitive bacterial species.
authors.affiliation: Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Germany. sayed.auda@yahoo.com.|Department of Pharmaceutics and Industrial Pharmacy, Faculty of pharmacy, Al-Azhar, University, Assuit branch, Assuit, Egypt. sayed.auda@yahoo.com.
authors.forename: Sayed H
authors.initials: SH
authors.lastname: Auda
authors.affiliation: Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Knütter
authors.affiliation: Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Bretschneider
authors.affiliation: Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Germany. matthias.brandsch@biozentrum.uni-halle.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brandsch
authors.affiliation: Institute of Applied Dermatopharmacy, Martin-Luther-University Halle-Wittenberg, Germany.
authors.forename: Yahya
authors.initials: Y
authors.lastname: Mrestani
authors.affiliation: Institute of Biology/Microbiology, Martin-Luther-University Halle-Wittenberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Große
authors.affiliation: Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Germany. reinhard.neubert@pharmazie.unihalle.de.
authors.forename: Reinhard H H
authors.initials: RH
authors.lastname: Neubert
keywords: Caco-2; antibacterial activity; cefadroxil; metal ions; transepithelial flux