Study on the pharmacokinetics of cefepime (I)

Abstract

The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), were studied in rats upon both single and repeated intravenous administration. 1. Blood level of radioactivity was 59.27 micrograms eq./ml at 5 minutes after single intravenous administration at a dose of 20 mg/kg, and declined biexponentially thereafter. The values of AUC and T 1/2 were 70.1 micrograms eq..hr/ml and 38.0 hours, respectively. 2. Blood level of radioactivity was 59.41 micrograms eq./ml at 5 minutes after administration on the 7th day of repeated intravenous administration at a daily dose of 20 mg/kg, and declined more slowly as compared to the case of single administration. The values of AUC and T 1/2 after repeated administration were 159.7 micrograms eq..hr/ml and 44.5 hours, respectively. 3. Urinary and fecal excretion rates after single administration were 93.3% and 3.3%, respectively. 4. Urinary and fecal excretion rates were almost constant throughout the repeated administration; 88.4-90.7% and 2.3-3.7%, respectively. 5. 14C-CFPM distributed rapidly to the whole body except to the central nervous system. Although the radioactivity was removed rapidly from tissues, high levels of radioactivity remained in the kidney and the spleen as compared to other tissues. 6. Tissue concentrations of radioactivity at 5 minutes after the final dose of repeated administration were about the same as those after single administration but they declined more slowly than those after single administration. High levels of radioactivity were found in the kidney and the spleen as were found upon single administration. The ratios of these levels between repeated and single dosing were 4.3 and 2.6 for kidney and spleen, respectively. 7. Data obtained with autoradiograms of the whole body were consistent with measured tissue distribution obtained in both cases of single and repeated administration.