Pharmacokinetics of cefepime during continuous venovenous hemodiafiltration

The objective of this study was to analyze the pharmacokinetics of cefepime, in six patients with acute renal failure related to septic shock, during continuous venovenous hemodiafiltration (CVVHD) (Hemospal AN 69S hemofilter; Hospal, Lyon, France). Six patients, mean age 65 +/- 4 years (range, 61 to 69), were included and each received 2 g of cefepime by intravenous infusion over a 30-min period every 12 h. Prefilter serum, dialysate outlet (DO), and ultrafiltrate samples were collected 0.47, 0.50, 0.57, 1, 3, 5, 7, and 12 h after the beginning of infusion. The time design of samples was optimized in accordance with the theory of D optimality. The cefepime concentrations were measured by high-performance liquid chromatography. The pharmacokinetics computation was carried out using P-PHARM software. Mean serum concentration peaks were 53 +/- 21.9 mg/liter (range, 13.0 to 68.9) one-half hour after the infusion. The mean elimination half-life was 8.11 +/- 2.22 h (range, 4.76 to 10.84). DO clearance was 66.57 +/- 30.14 ml/min (range, 38.66 to 119.87). The mean volume of distribution was 0.71 +/- 0.37 liters/kg of body weight. CVVHD was effective for cefepime elimination. In these subjects, the elimination half-life and DO clearance were almost constant. The results of this study suggested that a 2-g twice-daily infusion (usual dosage) was required for an effective concentration in this group of patients.