Interaction of Quinolones with Metal Cations in Aqueous Solution

概要

論文の詳細を見る
Quinolones are a group of potent antibacterial agents. Many reports show that oral absorption of quinolones is reduced by coadministration of metallic preparations. For better understanding of this phenomenon, we investigated the complex formations of quinolones (DU-6859a, DV-7751a, DR-3862,levofloxacin) with various metal cations by pH titrations, NMR and spectrophotometry. Several metal complexes including hydroxo species were confirmed by pH titrations. The order of stability constants among trivalent metal cations was Fe^<3+>>Al^<3+>, and those among devalent metal cations was Cu^<2+>>Fe^<2+>>Zn^<2+>>Mg^<2+>>Ca^<2+>. The differences in stability constants among quinolones were not as large. Complex structures and metal complex formation equilibria in aqueous solution were proposed. Quinolones were belived to bind metal cations through carboxyl group and carbonyl group of the quinolone ring, and these equilibria show that there are two types of deprotonation reactions from metal complex : the several Fe^<3+> complexes and Al^<3+> complexes liberate protons from coordinated water molecules under acidic to neutral conditions, while the other complexes liberate protons from amine groups under neutral to alkaline conditions. Moreover, quantitative behavior of metal complex in aqueous solution has been demonstrated by simulation for the first time. The simulation especially showed that quinolones interact with Al^<3+> in the stomach, but with Mg^<2+> in the intestines when coadministered with antacid containing Al^<3+> and Mg^<2+>. These results suggest that the complex formation of quinolones with metal cations is an important factor affecting absorption of the former in the gastrointestinal tract.
公益社団法人日本薬学会の論文
1996-08-15

Interaction of Quinolones with Metal Cations in Aqueous Solution

スポンサーリンク

概要

著者

関連論文

スポンサーリンク