RT Journal Article
SR Electronic
T1 Disposition of the cephalosporin cefepime in normal and renally impaired subjects.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 68
OP 73
VO 19
IS 1
A1 R H Barbhaiya
A1 C A Knupp
A1 S T Forgue
A1 G R Matzke
A1 C E Halstenson
A1 J A Opsahl
A1 K A Pittman
YR 1991
UL http://dmd.aspetjournals.org/content/19/1/68.abstract
AB 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.