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Clinical Pharmacokinetics

, Volume 56, Issue 12, pp 1441–1460 | Cite as

Clinical Pharmacokinetics and Pharmacodynamics of Colistin

  • Nicolas Grégoire
  • Vincent Aranzana-Climent
  • Sophie Magréault
  • Sandrine Marchand
  • William Couet
Review Article

Abstract

In this review, we provide an updated summary on colistin pharmacokinetics and pharmacodynamics. Colistin is an old molecule that is frequently used as last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Colistin is a decapeptide administered either as a prodrug, colistin methanesulfonate (CMS), when used intravenously, or as colistin sulfate when used orally. Because colistin binds to laboratory materials, many experimental issues are raised and studies on colistin can be tricky. Due to its large molecular weight and its cationic properties at physiological pH, colistin passes through physiological membranes poorly and is mainly distributed within the extracellular space. Renal clearance of colistin is very low, but the dosing regimen should be adapted to the renal function of the patient because CMS is partly eliminated by the kidney. Therapeutic drug monitoring of colistin is warranted because the pharmacokinetics of colistin are very variable, and because its therapeutic window is narrow. Resistance of bacteria to colistin is increasing worldwide in parallel to its clinical and veterinary uses and a plasmid-mediated resistance mechanism (MCR-1) was recently described in animals and humans. In vitro, bacteria develop various resistance mechanisms rapidly when exposed to colistin. The use of a loading dose might reduce the emergence of resistance but the use of colistin in combination also seems necessary.

Notes

Compliance with Ethical Standards

Funding

No support was received for the preparation of this manuscript.

Conflicts of interest

Nicolas Grégoire, Vincent Aranzana-Climent, Sophie Magréault, Sandrine Marchand and William Couet declare that they have no conflicts of interest.

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Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.INSERM U1070PoitiersFrance
  2. 2.Université de Poitiers, UFR Médecine-PharmaciePoitiersFrance
  3. 3.CHU PoitiersPoitiersFrance

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