Pharmacokinetics of cefepime in subjects with renal insufficiency.
The pharmacokinetics of intravenously administered cefepime (1000 mg over 30 minutes) were studied in 5 healthy volunteers and 20 patients with various degrees of renal impairment. Cefepime concentrations in plasma, urine, and hemodialysate were assayed using reverse-phase HPLC with ultraviolet detection. Mean peak plasma concentrations of cefepime at the end of 30-minute infusion ranges from 63.5 to 73.9 micrograms/ml and were not affected by the degree of renal impairment. The half-life of cefepime was approximately 2.3 hours in subjects with normal kidney function; it increased proportionately as renal function decreased. Significant linear relationships between total body clearance and creatinine clearance, as well as renal clearance and creatinine clearance, were observed. The mean volume of distribution at steady state in healthy volunteers was 20.5 liters and was not significantly altered in subjects with renal insufficiency. The mean cumulative urinary recovery of cefepime in healthy volunteers was 82.9% of the administered dose and significantly decreased in subjects with creatinine clearance less than 30 ml/min. Hemodialysis significantly shortened the elimination half-life from 13.5 hours during the predialysis period to 2.3 hours during the dialysis period. Cefepime dosage should be reduced in proportion to the decline in creatinine clearance.
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Syracuse, NY 13221.
R H
RH
Barbhaiya
C A
CA
Knupp
S T
ST
Forgue
G R
GR
Matzke
D R
DR
Guay
K A
KA
Pittman
D000328:Adult; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000378:metabolism; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008433:Mathematics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis
D002511:Cephalosporins; D000077723:Cefepime; D003404:Creatinine