Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys
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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.
KEY WORDScolistin nebulization pharmacokinetic modelling scintigraphy
- 99m Tc-DTPA
99m technetium-diethylene triamino pentaacetic acid
Area under the ELF concentrations-time curve
Colistin base activity
Epithelial lining fluid
Geometric standard deviation
High-performance liquid chromatography
Liquid chromatography coupled with tandem mass spectrometry
Lower limit of quantification
Mass median aerodynamic diameter
Non-linear mixed effects
Objective function value
Regions of interest
Visual predictive checks
ACKNOWLEDGMENTS AND DISCLOSURES
The authors thank Georges Roseau for its technical assistance in this study.
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