Use Of Colistin Serum Concentrations After Intravenous Administration Of Colistimethate Sodium To Determine Pharmacokinetic And Pharmacodynamic Relationships

Abstract

Purpose: To define the pharmacokinetics of colistin after colistimethate sodium infusion and use clinical and microbiological data to explore pharmacodynamic relationships between colistin plasma levels, clinical and microbiological outcomes and drug-related toxicities. Research Design: Multi-center, prospective, open-label, un-controlled observational study. Methodology/Technical Approach: Five plasma samples from 60 patients 18 years of age receiving colistimethate sodium will be collected, frozen and shipped to Ordway Research Institute where they will be analyzed using a liquid chromatography/mass spectrometry/mass spectrometry system to determine free and protein bound levels of colistin A and colistin B. This data will be used to generate pharmacokinetic models. Additionally, clinical data (to include Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE) score, lab values) of enrolled patients, and results of susceptibility testing on Gram negative bacterial isolates will be collected. The pharmacokinetic, clinical and microbiological data will be analyzed using Monte Carlo population modeling to explore pharmacodynamic relationships between plasma levels of colistin and clinical outcomes, microbiological outcomes and drug toxicities. This project is approved, but we will be unable to complete it as our collaborating lab, Ordway Research has closed and our local use of colistin has dropped to the point that we would be unable to achieve our enrollment goals.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2011
Accession Number
ADA555942

Entities

People

  • David Byers

Organizations

  • Henry M. Jackson Foundation for the Advancement of Military Medicine

Tags

DTIC Thesaurus Topics

  • Anti-Infective Agents
  • Bacterial Infections
  • Biomedical Research
  • Diseases And Disorders
  • Electronic Mail
  • Gram-Negative Bacterial Infections
  • Health Services
  • Infection
  • Infection Control
  • Liquid Chromatography
  • Mass Spectrometry
  • Military Medicine
  • Pharmacokinetics
  • Test And Evaluation
  • Toxicity
  • Wound Infections
  • Wounds And Injuries

Fields of Study

  • Medicine

Readers

  • Analytical Chemistry
  • Applied Combinatorial Optimization and Logic Circuit Design.
  • Toxicology/Environmental Toxicology