Effect of metal ions on the in vitro availability of enoxacin, its in vivo implications, kinetic and antibacterial studies

Abstract

Recebido em 10/10/09; aceito em 17/8/10; publicado na web em 7/1/11The present paper describes the effect of metals ions on the in vitro availability of enoxacin (a second generation quinolone antibiotic) owing to drug-metal interaction. These interaction studies were performed at 37 °C in different pH environments simulating human body compartments and were studied by UV spectroscopic technique. In order to determine the probability of these reactions different kinetic parameters (dissolution constants (K) and free energy change (∆G)) for these reactions were also calculated. It is proposed that the structure of enoxacin contains various electron donating sites which facilitate its binding with metallic cations forming chelates. Hence taking food products, nutritional supplements or multivitamins containing multivalent cations at the same time as enoxacin, could reduce the absorption of the drug into the circulation and thus would decrease the effectiveness of the drug. In addition, the MIC of enoxacin for various microorganisms before and after interaction with metal ions was calculated which in most cases was increased which possibly could impair the clinical efficacy of the drug.

Studies on intestinal passage of flumequine and oxytetracycline-loaded MIL-100 (Fe) in the presence of divalent ions

“…In the present study, the antibiotics FLM and OTC were protected from divalent ions that hinder their intestinal absorptions by the formation of non-absorbable chelates through their encapsulation in MIL-100 (Fe). Indeed, available literature has shown that simultaneous production of quinolones with Ca 2+ , Mg 2+ , Al 3+ leads to the formation of complexes [17] that reduce their intestinal absorptions, and thus their antibacterial activities [15]. This phenomenon of chelation by metal ions is also observed with tetracycline [3,4].…”

Analysis of Complexation Interactions between Metal Ions and Drugs under Pseudo-physiological pH Conditions by a High-throughput Screening Method Using a Solid-phase Extraction Cartridge

“…These complexes interfere substantially with the intestinal absorption of the drug because of the lower solubility of the metal-complex in the intestinal tract. [3][4][5] Moreover, metal complexes of some drugs, such as antibacterial and antiviral agents, show stronger activities than their free-forms, [6][7][8][9][10][11][12][13] perhaps due to the metal ion stabilized drug binding with the target microbial DNA. [8][9][10][11] Metal complexes of the above drugs form under physiological pH and ionic strength conditions.…”

Synthesis Characterization and Antimicrobial Activities of Azithromycin Metal Complexes

“…Therefore, as part of our continuous efforts focused on the in vitro activity of cephalosporins in presence of essential and trace elements [16][17][18], fluoroquinolone interactions with essential and trace elements [19][20][21][22][23][24] and macrolides including clarithromycin and erythromycin synergism [25,26] and roxithromycin antagonism [27] with essential and trace elements impelled us to study the antibacterial and antifungal activities of newly synthesized essential metal complexes of azithromycin. These complexes were synthesized as later are already present in our body and food or may be co-administered along with azithromycin as part of multivitamin combinations.…”