title: Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis.
abstract: Using nebulization to deliver aminoglycosides may be of benefit in cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa. However, one problem with this route is the absence of clinical parameters allowing estimation of the mass of drug deposited in the lungs (MDL). The aim of this study was to assess whether aminoglycoside excretion in the urine reflects the MDL. Fourteen studies were performed in seven CF patients. Amikacin was mixed with albumin labelled with 99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by the mass-balance technique. Urine was collected during the 24 h following inhalation and was assayed for amikacin by fluorescence polarization immunoassay (FPIA). The mean+/-SEM MDL was 14.0+/-2.2% of the nebulizer charge. The mean+/-SEM amount of amikacin excreted in the urine was 20.9+/-4.5 mg and correlated with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject variability in both deposition and excretion in the urine. Monitoring excretion of aminoglycosides in the urine allows noninvasive estimation of the mass of drug deposited in the lung in cystic fibrosis patients, which might be useful to assess the dose-response relationship in groups of patients, but intersubject variability prevents its use for individual follow-up.
authors.affiliation: Inserm EMI-U 00-10, University of Tours, Dept of Respiratory Diseases, Bretonneau University Hospital, France.
authors.forename: P F
authors.initials: PF
authors.lastname: Dequin
authors.forename: F
authors.initials: F
authors.lastname: Faurisson
authors.forename: E
authors.initials: E
authors.lastname: Lemarié
authors.forename: F
authors.initials: F
authors.lastname: Delatour
authors.forename: S
authors.initials: S
authors.lastname: Marchand
authors.forename: C
authors.initials: C
authors.lastname: Valat
authors.forename: E
authors.initials: E
authors.lastname: Boissinot
authors.forename: C
authors.initials: C
authors.lastname: de Gialluly
authors.forename: P
authors.initials: P
authors.lastname: Diot
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male
chemical_list: D000336:Aerosols; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents