Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys
2015 (English)In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 32, no 10, 3403-3414 p.Article in journal (Refereed) Published
The objective of this study was to compare two different nebulizers: Eflow rapidA (R) and Pari LC starA (R) 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 LCA (R) star than with Eflow RapidA (R) 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 starA (R) than the Eflow rapidA (R) 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 StarA (R) than with the Eflow RapidA (R) system.
Place, publisher, year, edition, pages
2015. Vol. 32, no 10, 3403-3414 p.
colistin, nebulization, pharmacokinetic modelling, scintigraphy
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-264832DOI: 10.1007/s11095-015-1716-0ISI: 000361720700023PubMedID: 26040660OAI: oai:DiVA.org:uu-264832DiVA: diva2:861868