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

Laura Whited, Meagan Grove, Dusten Rose, Nathaniel J. Rhodes, Marc H. Scheetz, J. Nicholas O'Donnell, Jessica Neeb, Kelli Thoele, David R. Jones, Christopher Lowe, Dawn Moore, Patrick J. Kiel

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1003-1010
Number of pages8
JournalPharmacotherapy
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Febrile Neutropenia
Cell Transplantation
Hematologic Neoplasms
Pharmacokinetics
Neoplasms
Transplants
cefepime
Germ Cell and Embryonal Neoplasms
Microbial Sensitivity Tests
Hematology
Serum
Intravenous Infusions
Population
Half-Life
Lymphoma
Leukemia
Prospective Studies

Keywords

  • cefepime
  • hematology
  • infectious disease
  • neutropenia
  • oncology
  • pharmacokinetics
  • transplant

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Pharmacokinetics of Cefepime in Patients with Cancer and Febrile Neutropenia in the Setting of Hematologic Malignancies or Hematopoeitic Cell Transplantation. / Whited, Laura; Grove, Meagan; Rose, Dusten; Rhodes, Nathaniel J.; Scheetz, Marc H.; O'Donnell, J. Nicholas; Neeb, Jessica; Thoele, Kelli; Jones, David R.; Lowe, Christopher; Moore, Dawn; Kiel, Patrick J.

In: Pharmacotherapy, Vol. 36, No. 9, 01.09.2016, p. 1003-1010.

Research output: Contribution to journalArticle

Whited, L, Grove, M, Rose, D, Rhodes, NJ, Scheetz, MH, O'Donnell, JN, Neeb, J, Thoele, K, Jones, DR, Lowe, C, Moore, D & Kiel, PJ 2016, 'Pharmacokinetics of Cefepime in Patients with Cancer and Febrile Neutropenia in the Setting of Hematologic Malignancies or Hematopoeitic Cell Transplantation', Pharmacotherapy, vol. 36, no. 9, pp. 1003-1010. https://doi.org/10.1002/phar.1807
Whited, Laura ; Grove, Meagan ; Rose, Dusten ; Rhodes, Nathaniel J. ; Scheetz, Marc H. ; O'Donnell, J. Nicholas ; Neeb, Jessica ; Thoele, Kelli ; Jones, David R. ; Lowe, Christopher ; Moore, Dawn ; Kiel, Patrick J. / Pharmacokinetics of Cefepime in Patients with Cancer and Febrile Neutropenia in the Setting of Hematologic Malignancies or Hematopoeitic Cell Transplantation. In: Pharmacotherapy. 2016 ; Vol. 36, No. 9. pp. 1003-1010.
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abstract = "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.",
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AU - Whited, Laura

AU - Grove, Meagan

AU - Rose, Dusten

AU - Rhodes, Nathaniel J.

AU - Scheetz, Marc H.

AU - O'Donnell, J. Nicholas

AU - Neeb, Jessica

AU - Thoele, Kelli

AU - Jones, David R.

AU - Lowe, Christopher

AU - Moore, Dawn

AU - Kiel, Patrick J.

PY - 2016/9/1

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N2 - 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.

AB - 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.

KW - cefepime

KW - hematology

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KW - oncology

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