Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys

Pharm Res. 2015 Oct;32(10):3403-14. doi: 10.1007/s11095-015-1716-0. Epub 2015 Jun 4.


Purpose: The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons.

Methods: Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization.

Results: Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system.

Conclusions: A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

Keywords: colistin; nebulization; pharmacokinetic modelling; scintigraphy.

Publication types

  • Comparative Study

MeSH terms

  • Aerosols / pharmacokinetics
  • Animals
  • Anti-Bacterial Agents / pharmacokinetics*
  • Chromatography, Liquid / methods
  • Colistin / analogs & derivatives*
  • Colistin / pharmacokinetics*
  • Female
  • Haplorhini / metabolism*
  • Lung / metabolism
  • Nebulizers and Vaporizers
  • Papio / metabolism*
  • Tandem Mass Spectrometry / methods


  • Aerosols
  • Anti-Bacterial Agents
  • colistinmethanesulfonic acid
  • Colistin