title: Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis (CVVHD) after intravenous administration of unadjusted dosage regimens.
  
  
  METHODS
  Two critically ill patients had eight blood samples collected during a 12 h interval on days 8 and 10 of polymyxin B therapy. Dialysate was collected every hour during the 12 h dosing interval. Polymyxin B binding in plasma was determined by rapid equilibrium dialysis. Concentrations of polymyxin B in plasma and dialysate samples were quantified using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay.
  
  
  RESULTS
  Respective maximum plasma concentrations in patients 1 and 2 were 8.62 and 4.38 mg/L; total body clearances (scaled linearly by body weight) were 0.043 and 0.027 L/h/kg, respectively, of which 12.2% and 5.62% were dialysis clearance, respectively. The corresponding volumes of distribution of polymyxin B at steady state were 0.50 and 0.34 L/kg, respectively, and protein binding in pooled plasma samples was 74.1% and 48.8%, respectively.
  
  
  CONCLUSIONS
  Our findings indicate that the recommended polymyxin B doses should not be reduced for patients on CVVHD.
authors.affiliation: Infectious Diseases Service,  Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre,  Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sandri
authors.forename: Cornelia B
authors.initials: CB
authors.lastname: Landersdorfer
authors.forename: Jovan
authors.initials: J
authors.lastname: Jacob
authors.forename: Márcio M
authors.initials: MM
authors.lastname: Boniatti
authors.forename: Micheline G
authors.initials: MG
authors.lastname: Dalarosa
authors.forename: Diego R
authors.initials: DR
authors.lastname: Falci
authors.forename: Tainá F
authors.initials: TF
authors.lastname: Behle
authors.forename: David
authors.initials: D
authors.lastname: Saitovitch
authors.forename: Jiping
authors.initials: J
authors.lastname: Wang
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Zavascki
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011112:Polymyxin B / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006435:Renal Dialysis / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D011112:Polymyxin B