title: Physicochemical compatibility of nebulizable drug admixtures containing colistimethate and tobramycin.
abstract: Inhalation therapy with nebulizable antibiotic drugs is a mainstay in treating Pseudomonas aeruginosa infections in cystic fibrosis patients. The combination of tobramycin and colistin was found to be superior to monotherapy in killing P. aeruginosa in biofilms. The simultaneous inhalation of tobramycin and colistin might be an option to increase the compliance of patients. The objective of this in-vitro study was to determine whether admixtures of inhalation solutions containing colistin methanesulfonate (CMS) and tobramycin are physicochemically compatible. Physical compatibility was determined by measuring pH and osmolality. Chemical compatibility was determined by testing the antibiotic activity of the mixtures by the pharmacopoeial microbiological assay and comparing the results to those of standard solutions. Samples were analyzed immediately after mixing and after 24 h. Values of pH and osmolality remained unchanged and in physiologically acceptable ranges. Neither for colistin methanesulfonate (CMS) nor for tobramycin losses of antibiotic potency were registered at any time. Admixtures of nebulizer solutions containing CMS and tobramycin were shown to be physicochemically compatible. Further investigations are needed to determine whether drug delivery is affected by mixing the nebulizer solutions to ensure that simultaneous inhalation is recommendable.
authors.affiliation: Department of Pharmacy, Johannes Gutenberg-University Medical Center, Mainz, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wollstadt
authors.forename: I
authors.initials: I
authors.lastname: Krämer
authors.forename: W
authors.initials: W
authors.lastname: Kamin
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D003091:Colistin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004338:Drug Combinations; D004344:Drug Incompatibility; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D009330:Nebulizers and Vaporizers; D009994:Osmolar Concentration; D019999:Pharmaceutical Solutions; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014031:Tobramycin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D019999:Pharmaceutical Solutions; C004691:colistinmethanesulfonic acid; D014031:Tobramycin; D003091:Colistin