{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:05:59Z","timestamp":1771045559395,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I\u2010neb device to the standard PARI\u2010LC Plus nebulizer in children with cystic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, open\u2010label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I\u2010neb (75\u00a0mg) and PARI\u2010LC Plus (300\u00a0mg). Study visits were separated by 1 month, in which 1 of the study nebulizers was used twice daily. Tobramycin PK for both nebulizers was established using measured tobramycin concentrations and Bayesian PK modelling software. Hearing and renal function tests were performed to test for aminoglycoside associated toxicity. In addition to standard estimated glomerular filtration rate values, biomarkers for tubular injury (KIM\u20101 and NAG) were measured. Patient and nebulizer satisfaction were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inhalations were well tolerated and serum trough concentrations below the predefined toxic limit were reached with no significant differences in PK parameters between nebulizers. Results of audiometry and estimated glomerular filtration rate revealed no abnormalities. However, increased urinary NAG\/creatinine ratios at visit 2 for both nebulizers suggest TIS\u2010induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I\u2010neb.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nebulization of 75\u00a0mg TIS with the I\u2010neb in children with cystic fibrosis resulted in comparable systemic exposure to 300\u00a0mg TIS with the PARI\u2010LC Plus and was well tolerated and preferred over the PARI\u2010LC Plus. Long\u2010term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13988","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T02:22:58Z","timestamp":1558491778000},"page":"1984-1993","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetics and safety of tobramycin nebulization with the I\u2010neb and PARI\u2010LC Plus in children with cystic fibrosis: A randomized, crossover study"],"prefix":"10.1111","volume":"85","author":[{"given":"Annelies J.","family":"van Velzen","sequence":"first","affiliation":[{"name":"Central Hospital Pharmacy  The Hague The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris W.F.","family":"Uges","sequence":"additional","affiliation":[{"name":"Central Hospital Pharmacy  The Hague The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry G.M.","family":"Heijerman","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, Haga Teaching Hospital  The Hague The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert G.M.","family":"Arets","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology University Medical Center Utrecht\u2010Wilhelmina Children's hospital  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Nuijsink","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology Haga Teaching Hospital\u2010Juliana Children's hospital  The Hague The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els C.","family":"van der Wiel\u2010Kooij","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, div Respiratory Medicine and Allergology Erasmus MC\u2010Sophia Children's Hospital, University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik M.","family":"van Maarseveen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gijsbert A.","family":"van Zanten","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bas","family":"Pullens","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Erasmus MC\u2010Sophia Children's Hospital, University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University of Groningen, University Medical Center 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