Abstract
Metabolic disposition of a new cephalosporin, DQ-2556, was studied during and after consecutive intravenous doses of 14C-labelled DQ-2556 once a day for 21 days.
1. The mean blood concentrations at 2h after each dose showed a steady-state plateau with a large standard deviation. However, those at 24h after each dose increased with time until the 18th dose reaching the plateau. After the last dose blood concentration initially declined smoothly, but later, at low concentration, it lasted longer than that observed in single dose study.
2. Tissue concentrations were nearly proportional to the blood concentration except in the spleen. The concentration in the spleen steadily increased during multiple dosing and reached to the same level as that of the kidney. Then, it sustained longer than that of blood.
3. After each dosing, more than 95 % of the dosed radioactivity was recovered in urine and the other part in feces during next 24h. Approximately 80% of the radioactivity excreted into urine was composed of DQ-2556.
4. These findings revealed that the metabolic disposition of DQ-2556 in multiple dosing could be characterized as repetition of that of single dosing except that a little amount of the drug and/or metabolites were excreted slowly.
