Pharmaceutical Research

, Volume 32, Issue 10, pp 3403–3414 | Cite as

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

  • Sandrine MarchandEmail author
  • Salim Bouchene
  • Michèle de Monte
  • Laurent Guilleminault
  • Jérôme Montharu
  • Maria Cabrera
  • Nicolas Grégoire
  • Patrice Gobin
  • Patrice Diot
  • William Couet
  • Laurent Vecellio
Research Paper



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.


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.


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.


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.


colistin nebulization pharmacokinetic modelling scintigraphy 


99m Tc-DTPA

99m technetium-diethylene triamino pentaacetic acid


Area under the ELF concentrations-time curve


Broncho-alveolar lavage


Central lung


Colistin base activity


Cystic fibrosis


Colistin methansulphonate


Epithelial lining fluid




Geometric standard deviation


High-performance liquid chromatography


Inter-individual variability




Inter-occasion variability




Liquid chromatography coupled with tandem mass spectrometry


Lower limit of quantification


Mass median aerodynamic diameter


Non-linear mixed effects


Objective function value


Peripheral lung




Regions of interest








Ventilator-associated pneumonia


Visual predictive checks



The authors thank Georges Roseau for its technical assistance in this study.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sandrine Marchand
    • 1
    • 2
    • 3
    Email author
  • Salim Bouchene
    • 4
  • Michèle de Monte
    • 5
  • Laurent Guilleminault
    • 5
  • Jérôme Montharu
    • 5
  • Maria Cabrera
    • 5
  • Nicolas Grégoire
    • 1
    • 2
  • Patrice Gobin
    • 1
    • 3
  • Patrice Diot
    • 5
  • William Couet
    • 1
    • 2
    • 3
  • Laurent Vecellio
    • 5
  1. 1.INSERM U-1070, Pôle Biologie SantéPoitiers Cedex 9France
  2. 2.Faculté de Médecine et de PharmacieUniversité de PoitiersPoitiers Cedex 9France
  3. 3.Laboratoire de Toxicologie et de PharmacocinétiqueCHU de PoitiersPoitiersFrance
  4. 4.Faculty of Pharmacy, Department of Pharmaceutical BiosciencesUppsala UniversityUppsalaSweden
  5. 5.Centre d’Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305Université de Tours, Faculté de MédecineToursFrance

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