title: Population pharmacokinetics of daptomycin in adult patients undergoing continuous renal replacement therapy.
abstract: The objective of this population pharmacokinetic (PK) analysis was to provide guidance for the dosing interval of daptomycin in patients undergoing continuous renal replacement therapy (CRRT).
  
  
  
  A previously published population PK model for daptomycin was updated with data from patients undergoing continuous veno-venous haemodialysis (CVVHD; n = 9) and continuous veno-venous haemodiafiltration (CVVHDF; n = 8). Model-based simulations were performed to compare the 24 h AUC, Cmaxand Cminof daptomycin following various dosing regimens (4, 6, 8, 10, and 12 mg kg-1every [Q] 24 h and Q48 h), with the safety and efficacy exposure references for Staphylococcus aureus bacteraemia/right-sided infective endocarditis.
  
  
  
  The previously developed daptomycin structural population PK model could reasonably describe data from the patients on CRRT. The clearance in patients undergoing CVVHDF and CVVHD was estimated at 0.53 and 0.94 l h-1, respectively, as compared with 0.75 l h-1in patients with creatinine clearance (CrCl) ≥ 30 ml min-1. Daptomycin Q24 h dosing in patients undergoing CRRT resulted in optimal exposure for efficacy, with AUC comparable to that in patients with CrCl ≥ 30 ml min-1. In contrast, Q48 h dosing was associated with considerably lower AUC24-48hin all patients for doses up to 12 mg kg-1and is therefore inappropriate.
  
  
  
  Q24 h dosing of daptomycin up to 12 mg kg-1provides comparable drug exposure in patients on CVVHD and in those with CrCl ≥ 30 ml min-1. Daily daptomycin use up to 8 mg kg-1doses are appropriate for patients on CVVHDF, but higher doses may increase the risk of toxicity.
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Charité Campus Mitte, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Khadzhynov
authors.affiliation: Department of Nephrology, Charité Campus Mitte, Charité - Universitätsmedizin, Berlin, Germany.|Dieter Scheffner Center for Medical Education and Educational Research, Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Harm
authors.initials: H
authors.lastname: Peters
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Chaves
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors.forename: Kamal
authors.identifier: 0000-0003-1896-9736
authors.initials: K
authors.lastname: Hamed
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors.forename: Micha
authors.initials: M
authors.lastname: Levi
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Zurich University Hospital, Zurich, Switzerland.
authors.forename: Natascia
authors.initials: N
authors.lastname: Corti
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003198:Computer Simulation; D017576:Daptomycin / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008954:Models, Biological; D006435:Renal Dialysis
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin
keywords: CRRT; CVVHD; CVVHDF; daptomycin; population pharmacokinetics; renal replacement therapy