Effect of Different Metal Ions on the Biological Properties of Cefadroxil

Pharmaceuticals

Sayed H. Auda⁴  Ilka Knütter¹  Beate Bretschneider⁴  Matthias Brandsch¹  Yahya Mrestani²  Cornelia Gro෾³ 

[1] Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, Germany;;Institute of Applied Dermatopharmacy, Martin-Luther-University Halle-Wittenberg, Germany;Institute of Biology/Microbiology, Martin-Luther-University Halle-Wittenberg, Germany;Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Germany

关键词: cefadroxil;    metal ions;    Caco-2;    transepithelial flux;    antibacterial activity;   

DOI  :  10.3390/ph2030184

来源: mdpi

【 摘 要 】

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 (K_i values 107 ± 23 and 19 ± 5 µM, respectively). Kinetic analysis showed that the K_t of Gly-Sar uptake was increased 2-fold in the presence of zinc sulphate (150 µM) whereas the V_max value 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.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.