Pharmacokinetics of cefepime in patients with the sepsis syndrome

• Published in: Journal of antimicrobial chemotherapy 1993-11, Vol.32 (suppl-B), p.117-122
• Main Authors: Kieft, H., Hoepelman, A. I. M., Knupp, C. A., van Dijk, A., Branger, J. M., Struyvenberg, A., Verhoef, J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aging - metabolism; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cefepime; Cephalosporins - administration & dosage; Cephalosporins - blood; Cephalosporins - pharmacokinetics; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Male; Medical sciences; Pharmacology. Drug treatments; Sepsis - drug therapy; Sepsis - metabolism; Spectrophotometry, Ultraviolet
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/32.suppl_B.117

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 iv. 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), T½ (3.4±l.l h), vdss (32.6±17.5 L), and the total clearance Cltotal (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 T½ in comparison with young healthy volunteers (T½ = 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 (T½ = 3.7 h). Cmax, AUC and Cltot were more variable than those observed in previous studies and are probably a reflection of the clinical conditions under which dosing and sampling occurred.