Pharmacokinetic and Pharmacodynamic Analyses of Ceftaroline in Adults with Cystic Fibrosis

摘要: tudy Objective To evaluate the pharmacokinetics and pharmacodynamics of ceftaroline in adults with cystic fibrosis (CF). Design Open-label, single-center, prospective study. Setting University-affiliated teaching institution. Patients Eight patients a diagnosis CF history methicillin-resistant Staphylococcus aureus who were treated between November 2013 September 2014. Intervention All received at least three doses intravenous 600 mg every 12 hours, administered as 60-minute infusion, to achieve steady-state concentrations before blood sample collection. After an interim analysis first four patients' pharmacokinetic data, remaining change dosage 8 hours. Measurements Main Results Patients' samples collected two time points, 2 6 hours after infusion initiation, administration ceftaroline. Serum determined by using validated mass spectrometry, lower limit detection 20 ng/ml. These used estimate patient-specific parameters, 10,000-patient Monte Carlo simulations performed determine pharmacodynamic probability target attainment (PTA) for CF. A PTA 90% or higher desired was considered adequate. The 60% dosing interval during which free (unbound) drug exceed minimum inhibitory concentration (%fT > MIC) simulated various MICs. Compared values previously reported other populations, volume distribution increased study patients, estimated half-life shorter. revealed that dose infused over 60 minutes, maintained than %fT MIC susceptibility breakpoint 1 mg/L. Conclusion The is altered CF, suggests need modified this patient population adequate MIC. should be fT