Pharmacokinetics of cefepime in patients with the sepsis syndrome

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 (Cl_Cr) was 55±8 mL/min. Mean±S.D. values for selected pharmacokinetic parameters on day 5 were C_max (94.2±23.9 mg/L), T_½ (3.4±l.l h), vd_ss (32.6±17.5 L), and the total clearance Cl_total (125±51 mL/min). Time to peak plasma concentration (T_max) 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 T_½ in comparison with young healthy volunteers (T_½ = 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 (T_½ = 3.7 h). C_max, 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.