Objectives For practical reasons, patients with cystic fibrosis (CF) tend to mix different inhalation solutions for concomitant inhalation instead of inhaling the different medications consecutively. A study was undertaken to examine the compatibility of colistimethate dissolved in 5.85% hypertonic sodium chloride (NaCl) solution and the quadripartite mixtures of colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate.
Methods The test solutions were prepared by mixing ordinary doses of the inhalation products and analysed immediately. Microbiological assays of antibiotics and high-performance liquid chromatography assays were used to determine chemical compatibility and visual inspection, pH and osmolality measurements were used to determine physical compatibility. Mixtures of colistimethate with NaCl solutions were stored in a refrigerator at 2–8°C for 48 h and retested.
Results The antimicrobial activity of colistimethate dissolved in 5.85% NaCl solution did not differ from the activity of colistimethate dissolved in 0.9% NaCl solution and remained unchanged over a period of 48 h. In the quadripartite admixtures the activity of colistimethate and the concentrations of ipratropium bromide, salbutamol sulfate and fluticasone-17-propionate amounted to ≥ 100% of the nominal concentrations. Chemical and physical compatibility was shown.
Conclusions When colistimethate is dissolved in 5.85% NaCl solution for inhalation, the antimicrobial activity remains unchanged over a period of 48 h. With regard to in vitro compatibility, simultaneous inhalation of quadripartite mixtures of colistimethate, fluticasone-17-propionate, salbutamol sulfate and ipratropium bromide or colistimethate in 5.85% NaCl solution is feasible but needs to be clinically confirmed.
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