Supervisors info:
Βαλσαμή Γεωργία, Αναπληρώτρια καθηγήτρια του Τομέα Φαρμακευτικής Τεχνολογίας, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Summary:
Over the last decade, the use of inhaled colistin in respiratory tract infections due to MDR Gram (-) pathogens has gained wide acceptance. In this study, the concentrations of colistin were determined in plasma and Epithelial lining fluid (ELF) samples of thirty mechanically ventilated patients with pulmonary infection.The patients received 2,000,000 IU of inhaled colistimethate sodium (CMS), using two types of nebulisers (Jet and Aeroneb). The analytical technique used to measure plasma and BAL/ELF colistin levels, was HPLC with fluorescence detector (HPLC-RF). The basic pharmacokinetic parameters of inhaled colistin were, also, determined bynon-compartmental analysis using Phoenix WinNonlin® 8.1 software. In the majority of patients, the concentrations observed in ELF samples were significantly higher than those in plasma, but in both cases, they were below the EUCAST clinical breakpoints for Acinetobacter baumannii και Klebsiella pneumonia. The average Tmax was 4-6 hours in ELF and 1-2 hours in plasma samples. Furthermore, the Tmax,MEAN and Cmax,MEAN in plasma were found 2.47±0.79h 1.55±2.18 μg/ml respectively for the patients who received the drug with Jet nebulizer, whereas for those patients in whom nebulization was performed with Aeroneb nebulizer, the corresponding values were Tmax=1.89±0.86h και Cmax=3.14±1.72 μg/ml. Further studies are required in larger number of patients and preferably at steady state conditions, in order to end up with more solid conclusions regarding pharmacokinetics of inhaled colistin.
Keywords:
colistin, ICU, ELF, nebulizer, pharmacokinetics