title: Multiple-dose pharmacokinetics of amikacin and ceftazidime in critically ill patients with septic multiple-organ failure during intermittent hemofiltration.
abstract: The pharmacokinetic parameters of amikacin and ceftazidime were assessed in four patients undergoing hemofiltration for septic shock. The parameters were assessed during hemofiltration and in the interim period. The concentration-time profiles of these two drugs in plasma, urine, and ultrafiltrate were investigated after intravenous perfusion (30 min). In all cases a 1-g dose of ceftazidime was administered; for amikacin, the dosage regimen was adjusted according to the patient's amikacin levels (250 to 750 mg). Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection for ceftazidime and by enzyme multiplied immunoassay for amikacin. The elimination half-life (t1/2) and the total clearance of amikacin ranged from 31.1 to 138.2 h and from 5.4 to 8.9 ml/min, respectively, during the interhemofiltration period in anuric patients. Hemofiltration substantially decreased the t1/2 (3.5 +/- 0.49 h) and increased the total clearance (89.5 +/- 11.8 ml/min). The hemofiltration clearance of amikacin represented 71% of the total clearance, and the hemofiltration process removed, on average, 60% of the dose. During hemofiltration, the elimination t1/2 of ceftazidime (2.8 +/- 0.69 h) was greatly reduced and the total clearance increased (74.2 +/- 11.2 ml/min) compared with those in the interhemofiltration period (9 to 43.7 h and 7.4 to 16.8 ml/min, respectively). About 55% of the administered dose was recovered in the filtrate, and the hemofiltration clearance of ceftazidime was 46 +/- 14.3 ml/min. A redistribution phenomenon (rebound) in the amikacin and ceftazidime concentrations in plasma (35 and 28%, respectively) was reported after hemofiltration in two patients. The MICs for 90% of the most important pathogens were exceeded by the concentrations of the two drugs in plasma during the whole treatment of these patients.
authors: Laboratoire de Pharmacocinétique, Pharmacie Carémeau, Centre Hospitalier Universitaire, Nimes, France.
authors: J M
authors: JM
authors: Kinowski
authors: J E
authors: JE
authors: de la Coussaye
authors: F
authors: F
authors: Bressolle
authors: D
authors: D
authors: Fabre
authors: G
authors: G
authors: Saissi
authors: O
authors: O
authors: Bouvet
authors: M
authors: M
authors: Galtier
authors: J J
authors: JJ
authors: Eledjam
mesh_terms: D000328:Adult; D000368:Aged; D000583:Amikacin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002442:Ceftazidime / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003422:Critical Care; D004334:Drug Administration Schedule; D005260:Female; D006440:Hemofiltration; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000150:complications*; D012772:Shock, Septic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D012984:Software
chemical_list: D000583:Amikacin; D002442:Ceftazidime