title: Pharmacokinetics of cefepime in patients with the sepsis syndrome.
abstract: We investigated the pharmacokinetics of cefepime after administration of multiple doses to seven patients with the sepsis syndrome. Patients ranged in age from 66 to 78 years (mean +/- S.D.: 74 +/- 5 years); all fulfilled the criteria of the sepsis syndrome and had APACHE-II scores between 14 and 21 (mean +/- S.D.: 17 +/- 2). Serial blood and urine samples were collected after a minimum of 3 days (steady state) of treatment with cefepime 2.0 g bd i.v. Cefepime was assayed by HPLC. Data were analysed using non-compartmental methods. The mean +/- S.D. creatinine clearance (Clcr) was 55 +/- 8 mL/min. Mean +/- S.D. values for selected pharmacokinetic parameters on day 5 were Cmax (94.2 +/- 23.9 mg/L), T1/2 (3.4 +/- 1.1 h), Vdss (32.6 +/- 17.5 L), and the total clearance Cl(total) (125 +/- 51 mL/min). Time to peak plasma concentration (Tmax) and area under curve (AUC) averaged 0.7 +/- 0.2 h and 305 +/- 115 mg.h/L, respectively. Cefepime plasma concentrations were above the MIC90 for Pseudomonas aeruginosa (7 mg/L) for approximately 80% of the time and in the case of Enterobacteriaceae (0.5 mg/L) for 100% of the time. The more prolonged T1/2 in comparison with young healthy volunteers (T1/2 = 2.1 h) is consistent with the changes in renal function associated with increased age, and is comparable to data obtained in healthy elderly subjects (T1/2 = 3.7 h). Cmax, AUC and Cl(tot) were more variable than those observed in previous studies and are probably a reflection of the clinical conditions under which dosing and sampling occurred.
authors.affiliation: Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Kieft
authors.forename: A I
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: C A
authors.initials: CA
authors.lastname: Knupp
authors.forename: A
authors.initials: A
authors.lastname: van Dijk
authors.forename: J M
authors.initials: JM
authors.lastname: Branger
authors.forename: A
authors.initials: A
authors.lastname: Struyvenberg
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002511:Cephalosporins; D000077723:Cefepime