title: Systemic absorption of nasally administered tobramycin and colistin in patients with cystic fibrosis.
abstract: OBJECTIVE
  In cystic fibrosis (CF) patients the paranasal sinuses can constitute a niche for bacteria, which can migrate to the lungs. Nasal administration of antibiotics may be effective, but safety of this treatment has to be established first. The objective of this study was to investigate the systemic absorption of nasally administered tobramycin, colistin (administered as colistin sulfomethate sodium; CMS) and a combination of both drugs using systemic absorption as surrogate for safety. In addition, tolerability of the nasal irrigations was examined.
  
  
  METHODS
  Ten adult CF patients performed three different nasal irrigations: 300 mg of tobramycin; 160 mg of CMS; and 300 mg of tobramycin combined with 160 mg of CMS. Serum concentrations of tobramycin and colistin A and B (the main components of colistin) were analysed. Tolerability was measured using a visual analogue scale. Dutch Trial Register: NTR 4008.
  
  
  RESULTS
  Following the tobramycin and the combined irrigation, only two patients had detectable tobramycin serum levels, with the highest being 0.054 mg/L. Serum levels of colistin A and B were not detectable. All three nasal irrigation solutions were well tolerated with a higher tolerability for CMS compared with tobramycin.
  
  
  CONCLUSIONS
  Nasal irrigations with tobramycin, CMS and a combination of tobramycin and CMS resulted in safe serum levels and were well tolerated.
authors.affiliation: Department of Pulmonology, Haga Teaching Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands m.berkhout@hagaziekenhuis.nl.
authors.forename: M C
authors.initials: MC
authors.lastname: Berkhout
authors.affiliation: Central Hospital Pharmacy, Escamplaan 900, 2547 EX The Hague, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: van Velzen
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: Department of Otorhinolaryngology, Haga Teaching Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands.
authors.forename: B M
authors.initials: BM
authors.lastname: de Kok
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Centre Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Fokkens
authors.affiliation: Department of Pulmonology, Haga Teaching Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands.
authors.forename: H G M
authors.initials: HG
authors.lastname: Heijerman
mesh_terms: D065567:Absorption, Physiological / Q000187:drug effects / Q000502:physiology*; D000281:Administration, Intranasal; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D003091:Colistin / Q000008:administration & dosage / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D014031:Tobramycin / Q000008:administration & dosage / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin; D003091:Colistin
keywords: antibiotics; nasal administration; pharmacokinetics