Pharmacokinetics of cefepime dihydrochloride arginine in subjects with renal impairment.
In this study, the safety, tolerance, and pharmacokinetics of a single 1-g intravenous dose of cefepime (BMY-28142) were investigated. Twenty-three volunteers with various degrees of renal function were assigned to four trial groups according to glomerular filtration rates (GFR). Group IV consisted of five patients with end-stage renal disease undergoing treatment with hemodialysis. Cefepime concentrations in samples from plasma, urine, and infusion solutions were assayed with high-pressure liquid chromatography. The volume of distribution corresponded to the assumed extracellular fluid volume and did not differ significantly between the four groups. The area under the concentration-time curve increased as renal function decreased; in group II (GFR, 31 to 80 ml/[min x 1.73 m2]; n = 6), it was already three times higher than in group I (GFR, > or = 80 ml/[min x 1.73 m2]; n = 5). Mean residence time was 2.4, 6.8, 11.4, and 31.6 h for the four groups, respectively. Total clearance decreased (97.2, 34.6, 19.8, and 6.3 ml/[min x 1.73 m2]) with decreasing renal function, and a linear relationship between total plasma clearance and GFR was found with the regression equation y = 0.92x-2.0 (r = 0.991). Renal clearance was linearly correlated to GFR with the regression equation y = 0.87x-6.1 (r = 0.989), indicating that renal elimination is mainly by glomerular filtration. During hemodialysis, the extraction ratios were between 0.40 and 0.65. Dialysis clearance varied between 69.9 and 94.6 ml/(min x 1.73 m2).
Cronqvist
J
J
Department of Infectious Diseases, University of Lund, Sweden.
Nilsson-Ehle
I
I
Oqvist
B
B
Norrby
S R
SR
D000328:Adult; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D011247:Pregnancy; D006435:Renal Dialysis
D002511:Cephalosporins; D000077723:Cefepime