Disposition of the cephalosporin cefepime in normal and renally impaired subjects.
The metabolism and disposition of an iv-administered, 1000 mg (100 microCi) single dose of the 14C-labeled cephalosporin cefepime was studied in healthy and renally impaired male volunteers. The 14C-label was located in the methyl group of the N-methyl pyrrolidine (NMP) moiety at the 3'-position of cefepime. Concentrations of cefepime and its metabolites were determined in plasma and urine as a function of time after drug administration. Cefepime comprised 95 and 76% of the total plasma radioactivity in subjects with normal and impaired renal functions, respectively. The elimination half-life of cefepime was 2 hr in normal volunteers and increased to 4 and 12 hr in subjects with moderate and severe renal impairment, respectively. Steady-state volume of distribution was about 18 liters and was independent of the degree of renal impairment. Cefepime was primarily excreted unchanged in the urine of normal subjects, as 87.9% of the total recovered radioactivity. The major cefepime metabolites, NMP N-oxide, the 7-epimer of cefepime and NMP, constituted 6.8, 2.5, and less than 1% of the total radioactivity excreted in urine, respectively. As the severity of renal impairment increased, the proportion of radioactivity recovered in urine as cefepime decreased and that of NMP-N-oxide increased. Our results indicate that cefepime undergoes minimal metabolism and is excreted primarily as unchanged drug in urine in humans with normal kidney functions.
Barbhaiya
R H
RH
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Syracuse, NY 13221-4755.
Knupp
C A
CA
Forgue
S T
ST
Matzke
G R
GR
Halstenson
C E
CE
Opsahl
J A
JA
Pittman
K A
KA
D000328:Adult; D001711:Biotransformation; D000077723:Cefepime; D002511:Cephalosporins / Q000378:metabolism / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008875:Middle Aged; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
D002511:Cephalosporins; D000077723:Cefepime