title: Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock.
abstract: BACKGROUND
  The purpose of the study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of piperacillin and tazobactam during high-volume haemodiafiltration (HVHDF).
  
  
  METHODS
  A single dose of piperacillin/tazobactam (4/0.5 g) was administered as 30 minute infusion during HVHDF to 10 patients with acute kidney injury due to septic shock. Arterial blood samples were collected before and at 30 or 60 min intervals over 8 h (12 samples) after study drug administration. Concentrations of piperacillin and tazobactam were determined by HPLC-MS/MS. R software was used for population PK analysis and Monte Carlo Simulation of probability of PK/PD target attainment (PTA) in 1000 subjects.
  
  
  RESULTS
  A total of 101 samples were collected during HVHDF. The median (IQR) estimated glomerular filtration rate of the patients was 16 (11.25-27.5) ml/min/1.73 m(2) and HVHDF effluent rate was 208 (146.3-298.3) ml/kg/h. A final two-compartment population PK model predicted mean (%SE) total piperacillin clearance on HVHDF was 6.9 (6.4) l/h, volume of distribution of central compartment 9.0 (10.1) l and of peripheral compartment 11.2 (12.2) l. The PTA of 50% fT>MIC for piperacillin 4 g/tazobactam 0.5 g dosed every 8 h as 0.5-h and 4-h infusion was 84.3% and 100% for MIC of 16 mg/l respectively. Aiming 100% fT>MIC of 16 mg/l, the PTA values were 88.6% and 61.0%, for piperacillin 4 g/tazobactam 0.5 g 4-h infusion every 6 and 8 h respectively.
  
  
  CONCLUSIONS
  For bactericidal PK/PD target attainment piperacillin/tazobactam doses of 4/0.5 g every 8 h appear appropriate in septic shock patients with minimal residual renal function during HVHDF.
authors.affiliation: Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.|Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Tamme
authors.affiliation: Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Oselin
authors.affiliation: Testing Centre, Institute of Chemistry, University of Tartu, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Kipper
authors.affiliation: Faculty of Mathematics and Computer Science, University of Tartu, Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Tasa
authors.affiliation: Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Metsvaht
authors.affiliation: Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.|Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia.
authors.forename: J
authors.initials: J
authors.lastname: Karjagin
authors.affiliation: Testing Centre, Institute of Chemistry, University of Tartu, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Herodes
authors.affiliation: Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.|Department of Anaesthesiology and Intensive Care, DRK Kliniken, Berlin, Köpenick, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kern
authors.affiliation: Clinic of Anaesthesiology and Intensive Care, Tartu University Hospital, Tartu, Estonia.|Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia.
authors.forename: J
authors.initials: J
authors.lastname: Starkopf
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D010878:Piperacillin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D012772:Shock, Septic / Q000628:therapy*; D065093:beta-Lactamase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin