Artículos
(Cu)II in vivo interaction with cefotaxime
Interacción in vivo del Cu(II) con cefotaxima
Antonio L. Doadrio
Department of Inorganic Chemistry and Bioinorganic. School of Pharmacy. University Complutense. Madrid. Spain.
Pilar Madrigal
Dirección Department of Toxicology and Legal Medicine. School of Medicine. University Complutense. Madrid. Spain
Juan de Dios Casas
Dirección Department of Toxicology and Legal Medicine. School of Medicine. University Complutense. Madrid. Spain
Abstract
The presence of Cu(II) in penicillin and cephalosporin solutions, has been proved, to promote in vitro the antibiotic degradation to the corresponding acid derivates. HPLC studies provided an additional evidence for the reaction mechanism. The mechanisms of Cu(II) catalysis involve a ternary complex. This work was undertaken to study the consequences of this degradation in vivo upper the pharmacokinetic, pharmacodynamic and activity of the antibiotic cefotaxime. It is one of the most used «third-generation» cephalosporin in the world, this is because of that the interaction cefotaxime-metal deserved our attention. Our results remarked a lower concentration of free cefotaxime in blood, liver, spleen, kidney, lung and heart in organs from animals suffering Cu-intoxication. The differences more significant between intoxicated and control rats were observed in liver, lung and kidney. In addition cefotaxime linked to copper lose most of the microbicidal activity against bacterial strains of Bacillus subtilis CECT 356, Escherichia coli CECT 434, Escherichia coli CECT 616, Staphilococus aureus spp aureus CECT 435, Staphilococus aureus spp aureus CECT 239, in plate tests. It means that cefotaxime would become ineffective as antibiotic in metal poisoned patients.
Keywords: Copper(II); Cefotaxime; Pharmacodynamic; Pharmacokinetic; HPLC.
Resumen
Este trabajo estudia la reacción del cobre II con una cefalosporina, la cefotoxima, in vivo; los mecanismos catalíticos que implican la presencia de complejos ternarios, su farmacocinética y su farmacodinamia que afectan a la actividad del antibiótico. Las diferencias más significativas entre las ratas intoxicadas y control fueron observadas en riñón, pulmón e hígado. También hemos estudiado la actividad microbicida en Bacillus subtilis CECT 356, Escherichia coli CECT 434, Escherichia coli CECT 616, Staphilococus aureus spp aureus CECT 435, Staphilococus aureus spp aureus CECT 239.
Palabras clave: Cobre(II); Cefotaxima; Farmacodinamia; Farmacocinética; HPLC.