Metabolic fate of cephacetrile after parenteral administration in rats and rabbits

1. The metabolic fate of 14C-cephacetrile was studied in rats and rabbits. The plasma level of intravenously injected cephacetrile decreased with half-lives of 17 and 22 minutes in rats and rabbits respectively, this decline being associated with a rapid appearance of the active metabolite, desacetylcephacetrile. Intramuscularly injected cephacetrile was rapidly absorbed by rats with a maximum plasma level at 20 minutes and a half-life of 16 minutes. Cephacetrile and desacetylcephacetrile did not enter erythrocytes. Cephacetrile was weakly bound to the plasma protein in the rat, rabbit and man. 2. Both in rats and rabbits, almost all of the injected radioactivity was excreted in the urine within 72 hours as the intact antibiotic and desacetylcephacetrile, only small amounts appearing in feces via bile. Neither the gamma-lactone of desacetyl-7-cyanacetamidocephalosporanic acid nor the violet-reddish pigment (CGP-695) produced from cephacetrile were detectable in the plasma or urine of the animals. 3. In rats given the labeled antibiotic intravenously, the radioactivity was widely distributed with concentrations being high in the kidney, plasma and liver, and lowest in the brain. The radioactivity crossed the rat placenta and appeared in the fetus. Radioactivity in these tissues disappeared as the plasma level declined. 4. During daily intramuscular injection of 14C-cephacetrile to rat, no significant changes were observed in the peak level of the plasma radioactivity or in the half-lives. In addition, dosing of the labeled antibiotic for 7 days caused no increase in tissue levels of radioactivity.