Effect of Different Metal Ions on the Biological Properties of Cefadroxil.docVIP

Pharmaceuticals 2009, 2, 184-193; doi:10.3390/ph2030184 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Article Effect of Different Metal Ions on the Biological Properties of Cefadroxil Sayed H. Auda 1,2,?, Ilka Knütter 3,?, Beate Bretschneider 1, Matthias Brandsch 3, Yahya Mrestani 4, Cornelia Gro?e 5 and Reinhard H. H. Neubert 1,* 1 Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Germany 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of pharmacy, Al-Azhar, University, Assuit branch, Assuit, Egypt; E-Mail: sayed.auda@ (S.H.A.) 3 Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Germany; E-Mail: matthias.brandsch@biozentrum.uni-halle.de (M.B.) 4 Institute of Applied Dermatopharmacy, Martin-Luther-University Halle-Wittenberg, Germany 5 Institute of Biology/Microbiology, Martin-Luther-University Halle-Wittenberg, Germany ? These authors contributed equally to this paper. * Author to whom correspondence should be addressed; E-Mail: reinhard.neubert@pharmazie.uni- halle.de; Tel.: +49-345-552-5000; Fax: +49-345-552-7292. Received: 9 October 2009; in revised form: 9 November 2009 / Accepted: 1 December 2009 / Published: 15 December 2009 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 (Ki values 107 ± 23 and 19 ± 5 μM, respectively). Kinetic analysis showed that the Kt of Gly-Sar uptake was increased 2-fold in the presence of zinc sulphate (150 μM) whereas the Vmax value were not affected suggesting that zinc ions inhibited Gly-Sar uptake by PEPT1 in a competitively manner. Ni2+ exhibited moderate inhibitor