PHARMACOKINETICS OF CEFEPIME DURING CONTINUOUS VENOVENOUS HEMODIAFILTRATION

The objective of this study was to analyze the pharmacokinetics of cef epime, in six patients with acute renal failure related to septic shoc k, 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 cefe pime by intravenous infusion over a 30-min period every 12 h. Prefilte r serum, dialysate outlet (DO), and ultrafiltrate samples were collect ed 0.47, 0.50, 0.57, 1, 3, 5, 7, and 12 h after the beginning of infus ion. The time design of samples was optimized in accordance with the t heory of D optimality. The cefepime concentrations were measured by hi gh-performance liquid chromatography. The pharmacokinetics computation was carried out using P-PHARM software. Mean serum concentration peak s 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 (rang e, 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 liter s/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.