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Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis

¹ Inserm EMI-U 00-10, University of Tours, Medical Intensive Care Unit and Dept of Respiratory Diseases, Bretonneau University Hospital, Tours, ² Inserm EMI-U 99-33, University of Paris 7, Paris, ³ Dept of Childhood Diseases and Cystic Fibrosis Unit, Clocheville University Hospital, Tours, and ⁴ Microbiology Laboratory, Trousseau University Hospital, Tours, France

CORRESPONDENCE: P. Diot, Service de Pneumologie, CHU Bretonneau, 37044, Tours, cedex 1, France. Fax: 33 247473882

Keywords: aerosol, aminoglycoside, cystic fibrosis, pharmacokinetics, urine

Received: September 30, 1999
Accepted April 11, 2001

This study was supported by Association Française de Lutte contre la Mucoviscidose.

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 polorization 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.

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