Interaction of Cefdinir with Iron in Aqueous Solution

Cefdinir (CFDN) is an orally active, semisynthetic cephalosporin antibiotic and its structure is characterized by an oxyimino side chain which is able to form complexes with various metal ions. We observed that bioavailability of CFDN in dogs was reduced when it was co-administered with iron(II) salts. To assess possible effects of extraneous iron such as iron supplements on the bioavailability of CFDN, stability constants of the complexes formed between CFDN and iron(II) and iron(III) have been determined in aqueous solution by potentiometric and spectrophotometric titration methods. The stability constants were as follows : log β110=7.53, log β120=14.44, log β130=18.33 for the iron(II) complexes and log β110=10.43, log β120=20.40 and log β130=27.54 for the iron(III) complexes. Theoretical species distribution diagrams as a function of pH for solutions of metal (M) (0.1 mM) and ligand (L) (0.3 mM) showed that M1L1H0 and M1L2H0 existed as major species for the iron(II) system and M1L2H0 and M1L3H0 were main species for the iron(III) system under neutral conditions. From these results it is believed that complex formation in the digestive tract is involved in the reduction of the bioavailability of CFDN in dogs. In addition, spectrophotometric studies indicated that iron(II) coordinated to CFDN via the thiazole-ring and deprotonated oxime nitrogen atoms and iron(III) coordinated via the amide and deprotonated oxime oxygen atoms.