title: Elimination of the piperacillin/tazobactam combination during continuous venovenous haemofiltration and haemodiafiltration in patients with acute renal failure.
abstract: The elimination of the piperacillin/tazobactam combination was studied in six patients with acute renal failure undergoing either continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF) at 1 L/h and 2 L/h for 12 h. Piperacillin 4 g/tazobactam 0.5 g was given iv on three successive treatment periods and their concentrations in plasma, ultrafiltrate/dialysate and urine were determined for 12 h after each dose. The elimination half-life of piperacillin during CVVH (7.7 +/- 2.3 h; mean +/- s.d.) was significantly longer than during CVVHDF 1 L/h (6.7 +/- 1.9 h) or 2 L/h (6.1 +/- 2.0 h) (P< 0.05). Corresponding values for tazobactam were 13.9 +/- 3.9, 11.6 +/- 3.3 and 9.4 +/- 2.4 h, respectively (P< 0.05). Total piperacillin clearance during CVVH (3.89 +/- 1.23 L/h) was significantly lower than during CVVHDF 1 L/h (5.06 +/- 1.68 L/h) or 2 L/h (5.48 +/- 2.11 L/h) (P< 0.05). The corresponding tazobactam clearance values were 2.42 +/- 0.75, 3.13 +/- 0.66 and 3.75 +/- 1.43 L/h, respectively. The mean 12 h elimination of piperacillin and tazobactam in ultrafiltrate/dialysate was 29% and 37% during CVVH, 42% and 57% during CVVHDF (1 L/h), and 46% and 69% during CVVHDF (2 L/h). We recommend 8 hourly dosing of patients with renal failure on CVVH or CVVHDF with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland. matti.valtonen@hus.fi
authors.forename: M
authors.initials: M
authors.lastname: Valtonen
authors.forename: E
authors.initials: E
authors.lastname: Tiula
authors.forename: O
authors.initials: O
authors.lastname: Takkunen
authors.forename: J T
authors.initials: JT
authors.lastname: Backman
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D017583:Hemodiafiltration / Q000379:methods / Q000706:statistics & numerical data; D006440:Hemofiltration / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010406:Penicillins / Q000493:pharmacokinetics / Q000627:therapeutic use; D010878:Piperacillin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000078142:Tazobactam
chemical_list: D004791:Enzyme Inhibitors; D010406:Penicillins; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin