Clinical Pharmacokinetics, Pharmacodynamics and Toxicodynamics of Polymyxins: Implications for Therapeutic Use

Roger L. Nation, Alan Forrest

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

16 Citations (Scopus)


The availability of sensitive, accurate and specific analytical methods for the measurement of polymyxins in biological fluids has enabled an understanding of the pharmacokinetics of these important antibiotics in healthy humans and patients. Colistin is administered as its inactive prodrug colistin methanesulfonate (CMS) and has especially complex pharmacokinetics. CMS undergoes conversion in vivo to the active entity colistin, but the rate of conversion varies from brand to brand and possibly from batch to batch. The extent of conversion is generally quite low and depends on the relative magnitudes of the conversion clearance and other clearance pathways for CMS of which renal excretion is a major component. Formed colistin in the systemic circulation undergoes very extensive tubular reabsorption; the same mechanism operates for polymyxin B which is administered in its active form. The extensive renal tubular reabsorption undoubtedly contributes to the propensity for the polymyxins to cause nephrotoxicity. While there are some aspects of pharmacokinetic behaviour that are similar between the two clinically used polymyxins, there are also substantial differences. In this chapter, the pharmacokinetics of colistin, administered as CMS, and polymyxin B are reviewed, and the therapeutic implications are discussed.

Original languageEnglish
Title of host publicationPolymyxin Antibiotics
Subtitle of host publicationFrom Laboratory Bench to Bedside
EditorsJian Li, Roger L. Nation, Keith S. Kaye
Place of PublicationSwitzerland
Number of pages31
ISBN (Electronic)9783030163730
ISBN (Print)9783030163716
Publication statusPublished - 1 Jan 2019

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • Clinical implications
  • Colistimethate
  • Colistin
  • Comparison of colistin and polymyxin B pharmacokinetics
  • Pharmacodynamics and toxicodynamics
  • Pharmacokinetics in humans
  • Polymyxin B

Cite this