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

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

Author information

1
INSERM U-1070, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France. sandrine.marchand@univ-poitiers.fr.
2
Faculté de Médecine et de Pharmacie, Université de Poitiers, 6 rue de la Milétrie, 86073, Poitiers Cedex 9, France. sandrine.marchand@univ-poitiers.fr.
3
Laboratoire de Toxicologie et de Pharmacocinétique, CHU de Poitiers, 2 rue de la Milétrie, 86000, Poitiers, France. sandrine.marchand@univ-poitiers.fr.
4
Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden.
5
Centre d'Etude des Pathologies Respiratoires, INSERM UMR 1100/EA6305, Université de Tours, Faculté de Médecine, 10 Boulevard Tonnellé, 37032, Tours, France.
6
INSERM U-1070, Pôle Biologie Santé, 1 Rue Georges Bonnet, TSA 51106, 86073, Poitiers Cedex 9, France.
7
Faculté de Médecine et de Pharmacie, Université de Poitiers, 6 rue de la Milétrie, 86073, Poitiers Cedex 9, France.
8
Laboratoire de Toxicologie et de Pharmacocinétique, CHU de Poitiers, 2 rue de la Milétrie, 86000, Poitiers, France.

Abstract

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

PMID:
26040660
DOI:
10.1007/s11095-015-1716-0
[Indexed for MEDLINE]

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