Individual Components of Polymyxin B Modeled via Population Pharmacokinetics to Design Humanized Dosage Regimens for a Bloodstream and Lung Infection Model in Immune-Competent Mice-Reference-Cited by-同舟云学术

Individual Components of Polymyxin B Modeled via Population Pharmacokinetics to Design Humanized Dosage Regimens for a Bloodstream and Lung Infection Model in Immune-Competent Mice

Published:2023-05-17 Issue:5 Volume:67 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Jiao Yuanyuan¹,Yan Jun²,Vicchiarelli Michael³,Sutaria Dhruvitkumar S.¹,Lu Peggy²,Reyna Zeferino²,Spellberg Brad⁴,Bonomo Robert A.⁵⁶⁷⁸⁹^ORCID,Drusano George L.³^ORCID,Louie Arnold³^ORCID,Luna Brian M.²^ORCID,Bulitta Jürgen B.¹^ORCID

Affiliation:

1. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA

2. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

3. Institute for Therapeutic Innovation, College of Medicine, University of Florida, Orlando, Florida, USA

4. Los Angeles County-USC (LAC+USC) Medical Center, Los Angeles, California, USA

5. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA

6. Deparment of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

7. Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA

8. Deparment of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA

9. Department of Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio, USA

Abstract

Polymyxin B is a “last-line-of-defense” antibiotic approved in the 1960s. However, the population pharmacokinetics (PK) of its four main components has not been reported in infected mice. We aimed to determine the PK of polymyxin B1, B1-Ile, B2, and B3 in a murine bloodstream and lung infection model of Acinetobacter baumannii and develop humanized dosage regimens.

Funder

HHS | U.S. Food and Drug Administration

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/aac.00197-23

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