Population pharmacokinetics of intravenous Polymyxin B from clinical samples

Christine J. Kubin, Brian C. Nelson, Cristina Miglis, Marc H. Scheetz, Nathaniel J. Rhodes, Sean N. Avedissian, Serge Cremers, Michael T. Yin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

A retrospective study was conducted in hospitalized patients receiving intravenous polymyxin B who underwent therapeutic drug monitoring during treatment. The aim of this study was to assess the population pharmacokinetics (PK) of intravenous polymyxin B in patients with variable total body weights and create a population model for clinical use. Nonlinear mixed-effects modeling analyses were performed. A total of 43 patients were included, and 70% of these patients were male. The median age was 58 years, and the median weight was 78 kg. The median polymyxin B dose was 180 mg/day or 2.8 mg/kg/day. A one-compartment model described the polymyxin B PK well with conditional mean parameter estimates of a clearance (CL) of 2.37 liters/h and a volume of distribution of 34.4 liters and can be employed for clinical population modeling. Total body weight was not significantly associated with CL (Akaike information criterion, 361.6 for the weight-based model versus 359.5 for the non-weight-based model). These data suggest that dosing according to patient body weight requires further exploration. Greater study is needed to assess the relationships between polymyxin B exposures and efficacy and toxicity.

Original languageEnglish (US)
Article numbere01493-17
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number3
DOIs
StatePublished - Mar 2018
Externally publishedYes

Keywords

  • Dosing
  • Polymyxin B
  • Polymyxins
  • Population PK

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Population pharmacokinetics of intravenous Polymyxin B from clinical samples'. Together they form a unique fingerprint.

Cite this