Pharmacokinetics of Cefepime in Patients with Cancer and Febrile Neutropenia in the Setting of Hematologic Malignancies or Hematopoeitic Cell Transplantation

STUDY OBJECTIVE To evaluate the steady-state pharmacokinetic parameters of standard cefepime dosing regimens in a hematologic malignancy and hematopoietic cell transplant patient population with febrile neutropenia. DESIGN Open-label, single-center, prospective pharmacokinetic study. SETTING National Cancer Institute-designated cancer center. PATIENTS Nine adults with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia and were admitted to a hematology-oncology service between January and July 2014. INTERVENTION Patients received empirical cefepime 2 g every 8 hours, administered as a 30-minute intravenous infusion, for febrile neutropenia. MEASUREMENTS AND MAIN RESULTS Steady-state cefepime serum concentrations were measured after at least 2 days of continuous therapy. Venous blood samples were intensively sampled between 0 and 8 hours after the start of the 30-minute infusion at steady state. Seven of the nine patients had a hematologic malignancy diagnosis of acute leukemia, lymphoma, or myeloma, and two patients had a germ cell tumor diagnosis. Noncompartmental analysis revealed mean +/- SD parameters as follows at steady state: area under the plasma concentration-time curve from 0-8 hours 222.9 +/- 72.9 mg hour/L, maximum concentration 120.9 +/- 21.8 mg/L, clearance 9.7 +/- 3.7 L/hour, apparent volume of distribution 19.2 +/- 4.65 L, and elimination half-life 1.4 +/- 0.3 hours. A one-compartment pharmacokinetic model identified a mean +/- SD volume of distribution of 20.9 +/- 1.3 L and an elimination rate constant of 0.39 +/- 0.03 hour(-1). The mean estimated percentage of time that drug concentration remains above the pathogen minimum inhibitory concentration (fT>MIC) in serum was 55%, 77%, and 99% at MICs of 16, 8, and 4 mg/L, respectively. CONCLUSION Patients with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia demonstrated homogeneous calculated cefepime volumes and clearances. The population parameters presented in this study may aid in the calculation of patient-specific fT>MIC for similar patients.