title: Pharmacokinetics of imipenem and cilastatin during continuous venovenous hemodialysis in patients who are critically ill.
abstract: The objective of this study is to study the pharmacokinetics of imipenem-cilastatin in patients with anuria related to multiorgan failure during continuous venovenous hemodialysis (CVVHD) at a fixed blood flow rate of 60 ml/min, fixed dialysate flow rate of 20 ml/min, and drainage flow rate of 1-3 mil/min. A prospective open label study was designed in an intensive care unit in a university hospital. Six patients who required mechanical ventilation and inotropic agents and exhibited acute anuric renal failure were examined. Intravenous imipenem-cilastatin, 500/500 mg, was administered over 30 mins. Blood samples were obtained from the inlet and the outlet of the dialyzer and dialysate samples from the outlet before and at 0.0, 0.5, 1.0, 2.0, 3.0, 6.0, 9.0, and 12.0 hrs after infusion ended. The peak and trough concentrations of imipenem were 32.47 +/- 6.69 micrograms/ml and 1.12 +/- 0.46 micrograms/ml, respectively, whereas those of cilastatin were 50.05 micrograms/ml +/- 14.80 and 9.53 +/- 3.25 micrograms/ml, respectively. The half life was 2.79 +/- 0.3 hr for imipenem, and 6.67 +/- 0.93 hr for cilastatin. Total body clearance of imipenem was 89.4 +/- 17.5 ml/min, including the clearance by CVVHD of 18.7 +/- 1.2 ml/min, and corresponding values for cilastatin were 31.7 +/- 9.0 ml/min and 13.7 +/- 3.4 ml/min. In conclusion, in patients with anuria, the elimination of imipenem-cilastatin was constant during CVVHD. The recommended regimen in patients with anuria who receive CVVHD in this setting was estimated as intravenous imipenem-cilastatin, 500/500 mg, every 12 hrs.
authors.affiliation: Department of Anesthesiology and Intensive Carer Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Sekimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D000368:Aged; D015377:Cilastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000493:pharmacokinetics*; D006435:Renal Dialysis; D013845:Thienamycins / Q000493:pharmacokinetics*
chemical_list: D011480:Protease Inhibitors; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem