title: Dry powder inhalation of colistin sulphomethate in healthy volunteers: A pilot study.
abstract: BACKGROUND
  Pulmonary administration of the antimicrobial drugs colistin sulphomethate and tobramycin has been shown to be effective in slowing down pulmonary deterioration in cystic fibrosis (CF) patients. Both drugs are administered by liquid nebulisation, a technique known to have disadvantages. Dry powder inhalation may be an attractive alternative. We investigated inhalation of colistin sulphomethate dry powder using a newly developed Twincer device in healthy volunteers.
  
  
  METHODS
  Eight healthy volunteers inhaled a single dose of 25mg colistin sulphomethate dry powder each, using the Twincer inhaler. The median diameter (X(50)) of the dry powder was 1.6 microm (X(10)=0.7 microm, X(90)=3.1 microm), measured by laser diffraction technique. Pulmonary function tests were performed before, 5 and 30 min after inhalation. Serum samples were drawn at t=15 min, 45 min, 1.5h, 2.5h, 3.5h, 5.5h, 7.5h and 24h after inhalation.
  
  
  RESULTS
  The colistin sulphomethate dry powder inhaler was well tolerated: no clinically relevant effect on FEV(1) was observed nor did the volunteers experience adverse effects.
  
  
  CONCLUSIONS
  Dry powder inhalation of colistin sulphomethate using the Twincer inhaler is well tolerated by healthy volunteers. A pilot study in cystic fibrosis patients is therefore considered safe in developing a dry powder inhalation of colistin for everyday CF treatment.
authors.affiliation: Apotheek Haagse Ziekenhuizen, The Hague, The Netherlands; Adult Cystic Fibrosis Center, Haga Teaching Hospital, The Hague, The Netherlands. Electronic address: e.westerman@ahz.nl.
authors.forename: E M
authors.initials: EM
authors.lastname: Westerman
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: de Boer
authors.affiliation: Apotheek Haagse Ziekenhuizen, The Hague, The Netherlands; Adult Cystic Fibrosis Center, Haga Teaching Hospital, The Hague, The Netherlands.
authors.forename: P P H
authors.initials: PPH
authors.lastname: Le Brun
authors.affiliation: Apotheek Haagse Ziekenhuizen, The Hague, The Netherlands; Adult Cystic Fibrosis Center, Haga Teaching Hospital, The Hague, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: Frijlink
authors.affiliation: Adult Cystic Fibrosis Center, Haga Teaching Hospital, The Hague, The Netherlands.
authors.forename: H G M
authors.initials: HGM
authors.lastname: Heijerman
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D003091:Colistin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D010865:Pilot Projects; D011208:Powders; D012016:Reference Values; D012129:Respiratory Function Tests; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; D003091:Colistin