GENERAL PHARMACOLOGY OF CEFEPIME

Abstract

General pharmacological properties of cefepime (CFPM), a new injectable semisynthetic cephalosporin and its metabolite N-methylpyrrolidine-N-oxide (NMP-N-oxide) were studied in laboratory animals.The results obtained are summarized as follows:
1. CFPM reduced spontaneous locomotor activity but potentiate the anesthesia at the highest dose in mice.Furthermore, significant hypothermia and analgesia were observed at the same dose in mice.No effects were found on the other CNS function in mice and rats or on EEG activities in rabbits.
2. Muscle relaxant activity was not observed in mice treated with CFPM even at the highest dose.
3. CFPM had no effect on the intestinal smooth muscle and did not show any antagonism against some smooth muscle contracting drugs.
4. The respiration, blood pressure, heart rate and ECG were affected by CFPM.Those changes, however, might have been principally caused by L-arginine blended with CFPM product.
5. No effect of CFPM on the intestinal movement or gastric secretion was found even at the highest dose of CFPM.
6. The pH neutralizer L-arginine caused alterations in the renal function and electrolyte metabolism but CFPM did not.
7. Whole blood clotting time tended to be lengthened by CFPM at the highest concentration but this effect seemed to have been caused by L-arginine.Other parameters of the coagulation system or red blood cell resisitance were not affected by CFPM.
8. NMP-N-oxide, a metabolite of CFPM, had almost no effect on any of the tested parameters except for its slight effect on the circulatory system.
These findings indicate that CFPM has scarcely any pharmacological properties which might be leading to severe adverse reactions in clinical use.