title: Pharmacokinetic and Pharmacodynamic Analyses of Ceftaroline in Adults with Cystic Fibrosis.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics and pharmacodynamics of ceftaroline in adults with cystic fibrosis (CF).
  
  
  METHODS
  Open-label, single-center, prospective study.
  
  
  METHODS
  University-affiliated teaching institution.
  
  
  METHODS
  Eight patients with a diagnosis of CF and a history of methicillin-resistant Staphylococcus aureus who were treated with ceftaroline between November 2013 and September 2014.
  
  
  METHODS
  All patients received at least three doses of intravenous ceftaroline 600 mg every 12 hours, administered as a 60-minute infusion, to achieve steady-state concentrations before blood sample collection. After an interim analysis of the first four patients' pharmacokinetic data, the remaining four patients received a change in dosage of ceftaroline to 600 mg every 8 hours.
  
  
  RESULTS
  Patients' blood samples were collected at two time points, 2 and 6 hours after infusion initiation, after administration of at least three doses of ceftaroline. Serum ceftaroline concentrations were determined by using a validated mass spectrometry, with a lower limit of detection of 20 ng/ml. These ceftaroline concentrations were used to estimate patient-specific pharmacokinetic parameters, and 10,000-patient Monte Carlo simulations were performed to determine the pharmacodynamic probability of target attainment (PTA) for ceftaroline in adults with CF. A PTA of 90% or higher for the desired pharmacodynamic target was considered adequate. The PTA for 60% or higher of the dosing interval during which free (unbound) drug concentrations exceed the minimum inhibitory concentration (%fT > MIC) was simulated for various MICs. Compared with values previously reported in other populations, the volume of distribution was increased in the study patients, and the estimated half-life was shorter. Monte Carlo simulations revealed that a dose of ceftaroline 600 mg every 8 hours, infused over 60 minutes, maintained a higher than 90% PTA for %fT > MIC of 60% or higher for an MIC at the susceptibility breakpoint of 1 mg/L.
  
  
  CONCLUSIONS
  The pharmacokinetics of ceftaroline is altered in adults with CF, which suggests the need for modified dosing in this patient population to achieve adequate %fT > MIC. A dosage of intravenous ceftaroline 600 mg every 8 hours administered as a 60-minute infusion should be considered to achieve 60% fT > MIC.
authors.affiliation: UK HealthCare Pharmacy Services, Lexington, Kentucky.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Autry
authors.affiliation: UK HealthCare Pharmacy Services, Lexington, Kentucky.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rybak
authors.affiliation: UK HealthCare Pharmacy Services, Lexington, Kentucky.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: Noelle R
authors.initials: NR
authors.lastname: Leung
authors.affiliation: UK HealthCare Pharmacy Services, Lexington, Kentucky.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Gardner
authors.affiliation: UK HealthCare Pharmacy Services, Lexington, Kentucky.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: Donna R
authors.initials: DR
authors.lastname: Burgess
authors.affiliation: Department of Pediatric Pulmonary Medicine, University of Kentucky College of Medicine, Lexington, Kentucky.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Anstead
authors.affiliation: UK HealthCare Pharmacy Services, Lexington, Kentucky.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kuhn
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline
keywords: ceftaroline; cystic fibrosis; methicillin-resistant Staphylococcus aureus; pharmacodynamics; pharmacokinetics