A simple tool for monitoring nebulized amikacin treatments based on a single urine assay

Aerosolized aminoglycosides have demonstrated their efficacy in the treatme nt of P. aeruginosa pneumonia in cystic fibrosis (CF) patients. There is wi de interpatient variability in the deposited and systemic drug doses that d epend on both the nebulization and inhalation conditions and result in a ri sk of inefficacy or toxicity. We have developed a tool to provide a simple method for individual dose monitoring by estimating the total quantity of a mikacin excreted, which corresponds to the dose absorbed systemically. It i s based on a single urine assay. Thirty-seven urinary pharmacokinetic time courses in healthy volunteers (groups A and B) or in CF patients (groups C and D) were used. The rules for extrapolating the total dose excreted on th e basis of 6-, 8-, 10-, and 12-h urine samples, were determined from group A. The accuracy of these rules was then tested in the other three groups. T he total amount excreted was poorly predictable, with a coefficient of vari ation (CV) of 36 and 30% in the healthy volunteers, and of 48 and 82% in th e CF group, whereas the CV of the estimated amount, based on 8- to 12-h sam ples, was only 10-15% in the healthy volunteers and 4-8% in the CF patients . Collecting a single sample over an 8- to 12-h period requires overnight s ampling. The very low circadian variations in renal function, ranging from -2% to +5%, demonstrated the absence of any significant bias resulting from overnight sampling. A single urine assay can therefore be proposed as a si mple, noninvasive, low cost, and reliable method for the clinical monitorin g of nebulized amikacin in CF patients. Further studies are needed before t his method can be extended to aerosol treatments with other aminoglycosides .