title: Safety and Tolerability of Nebulized Amoxicillin-Clavulanic Acid in Patients with COPD (STONAC 1 and STONAC 2).
abstract: The safety and tolerability of nebulized amoxicillin clavulanic acid were determined in patients with stable COPD and during severe exacerbations of COPD. Nine stable COPD patients received doses ranging from 50:10 mg up to 300:60 mg amoxicillin clavulanic acid and eight patients hospitalised for a COPD exacerbation received fixed doses 200/40 mg twice daily. Safety was evaluated by spirometry before and after inhalation. Tolerability was evaluated by questionnaire. Plasma and expectorated sputum samples were assayed for amoxicillin content. Seventeen patients underwent in total 100 nebulizations with amoxicillin clavulanic acid. In this safety and tolerability study no clinically relevant deteriorations in FEV1 were observed. Nebulized amoxicillin clavulanic acid produces sputum concentrations well above the Minimal Inhibiting Concentration of 90% for potential pathogenic micro-organisms, with low concentrations in the central compartment (low systemic exposure). Based on spirometry and reported side effects, inhalation of nebulized amoxicillin clavulanic acid seems to be safe and well tolerated, both in stable patients with COPD as in those experiencing a severe exacerbation. Levels of amoxicillin were adequate.
authors.affiliation: a Department of Clinical Pharmacy , Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: L C
authors.initials: LC
authors.lastname: Nijdam
authors.affiliation: b Department of Clinical Pharmacy , Ziekenhuisgroep Twente , Hengelo/Almelo, Enschede , the Netherlands.
authors.forename: M D M
authors.initials: MD
authors.lastname: Assink
authors.affiliation: c Department of Pulmonary Medicine , Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Kuijvenhoven
authors.affiliation: c Department of Pulmonary Medicine , Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: M E A
authors.initials: ME
authors.lastname: de Saegher
authors.affiliation: c Department of Pulmonary Medicine , Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: P D L P M
authors.initials: PD
authors.lastname: van der Valk
authors.affiliation: d Department of Research Methodology , Measurement, and Data Analysis, University of Twente , Enschede , the Netherlands.|e Medical School Twente, Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van der Palen
authors.affiliation: e Medical School Twente, Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: M G J
authors.initials: MG
authors.lastname: Brusse-Keizer
authors.affiliation: a Department of Clinical Pharmacy , Medisch Spectrum Twente , Enschede , the Netherlands.
authors.forename: K L L
authors.initials: KL
authors.lastname: Movig
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000032:analysis; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D013183:Sputum / Q000737:chemistry; D011795:Surveys and Questionnaires; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D019980:Amoxicillin-Potassium Clavulanate Combination
keywords: COPD; amoxicillin clavulanic acid; antibiotics; inhalation; nebulization