title: Single-dose daptomycin pharmacokinetics in chronic haemodialysis patients.
abstract: BACKGROUND
  Daptomycin has concentration-dependent antibacterial activity against Gram-positive bacteria. Its use is increasing in haemodialysis units. The manufacturer recommends a 4-6-mg/kg dose administered every 48 hrs for patients receiving haemodialysis. However, there are no published data about daptomycin pharmacokinetics and clearance during haemodialysis. The recommended dosing regimen would conflict with asymmetric thrice-weekly haemodialysis, which yields two ~44-hr and one ~68-hr interdialytic periods. This is the first study to evaluate daptomycin pharmacokinetics in haemodialysis patients, assess the extent of daptomycin dialytic removal and model serum concentrations at 44 and 68 hrs.
  
  
  METHODS
  Six otherwise healthy subjects on chronic haemodialysis (55.3 +/- 16.1 years old, three females, 66.2 +/- 14.2 kg) received a single 6-mg/kg dose of daptomycin post-haemodialysis infused over 30 minutes. Serial blood samples were collected for ~44 hrs (pre-next haemodialysis) and throughout the subsequent haemodialysis session with a high permeability haemodialyser. Individual pharmacokinetic parameters determined by compartmental analysis were used to model trough serum concentrations at 44 and 68 hrs with 6-, 8- and 10-mg/kg post-haemodialysis doses.
  
  
  RESULTS
  The haemodialysis session in this trial yielded mean urea and daptomycin reduction ratios of 79.6 +/- 5.8% and 57.6 +/- 9.2%, respectively. Daptomycin half-life was 19.4 +/- 6.5 and 3.8 +/- 1.1 hrs 'off' and 'on haemodialysis', respectively, with minimal rebound 1 hr post-haemodialysis. All modelled trough concentrations at 44 and 68 hrs at all doses exceed typical minimum inhibitory concentration (MIC(90)) values for Staphylococcus aureus and Enterococcus faecalis.
  
  
  CONCLUSIONS
  Daptomycin serum concentrations declined by ~50% after a 4-hr haemodialysis session with a high permeability haemodialyser. A 6-mg/kg i.v. post-haemodialysis thrice-weekly dose should result in sufficient pre-haemodialysis daptomycin serum concentrations even after a 68-hr interdialytic period.
authors.affiliation: University of Michigan College of Pharmacy, Department of Clinical, Social & Administrative Sciences, Ann Arbor, MI, USA.
authors.forename: Noha N
authors.initials: NN
authors.lastname: Salama
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Segal
authors.forename: Mariann D
authors.initials: MD
authors.lastname: Churchwell
authors.forename: Jignesh H
authors.initials: JH
authors.lastname: Patel
authors.forename: Lihong
authors.initials: L
authors.lastname: Gao
authors.forename: Michael
authors.initials: M
authors.lastname: Heung
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Mueller
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003198:Computer Simulation; D017576:Daptomycin / Q000493:pharmacokinetics*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000382:microbiology* / Q000628:therapy; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin