title: Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.
abstract: OBJECTIVE
  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.
authors.affiliation: INSERM U-1070, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France. sandrine.marchand@univ-poitiers.fr.|Faculté de Médecine et de Pharmacie, Université de Poitiers, 6 rue de la Milétrie, 86073, Poitiers Cedex 9, France. sandrine.marchand@univ-poitiers.fr.|Laboratoire de Toxicologie et de Pharmacocinétique, CHU de Poitiers, 2 rue de la Milétrie, 86000, Poitiers, France. sandrine.marchand@univ-poitiers.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchand
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden.
authors.forename: Salim
authors.initials: S
authors.lastname: Bouchene
authors.affiliation: Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: de Monte
authors.affiliation: Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Guilleminault
authors.affiliation: Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Montharu
authors.affiliation: Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Cabrera
authors.affiliation: INSERM U-1070, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France.|Faculté de Médecine et de Pharmacie, Université de Poitiers, 6 rue de la Milétrie, 86073, Poitiers Cedex 9, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Grégoire
authors.affiliation: INSERM U-1070, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France.|Laboratoire de Toxicologie et de Pharmacocinétique, CHU de Poitiers, 2 rue de la Milétrie, 86000, Poitiers, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Gobin
authors.affiliation: Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Diot
authors.affiliation: INSERM U-1070, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France.|Faculté de Médecine et de Pharmacie, Université de Poitiers, 6 rue de la Milétrie, 86073, Poitiers Cedex 9, France.|Laboratoire de Toxicologie et de Pharmacocinétique, CHU de Poitiers, 2 rue de la Milétrie, 86000, Poitiers, France.
authors.forename: William
authors.initials: W
authors.lastname: Couet
authors.affiliation: Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vecellio
mesh_terms: D000336:Aerosols / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D003091:Colistin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D000882:Haplorhini / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D010215:Papio / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin
keywords: colistin; nebulization; pharmacokinetic modelling; scintigraphy