Cefotaxime: sites and pathway of metabolic conversion.

This paper examines the metabolism of 14C-cefotaxime (14C-HR 756) in the rat and attempts to identify the metabolic events in this and other species. In rat desacetyl cefotaxime is usually the major excretion product and sole metabolite of cefotaxime. However, when renal elimination of this metabolite is prevented by bilateral nephrectomy, two further metabolites, the stereoisomeric opened beta-lactam ring forms of desacetyl cefotaxime lactone, are also produced. These metabolites are found in the urine of man and dogs dosed with cefotaxime. It is suggested that generation of these metabolites is dependent on formation of the lactone form of the desacetyl metabolite. Evidence is also presented showing that these metabolic conversions occur in the liver.