Cargando…

Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study

AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open‐label, crossover study was performed. In 2 separate study visits,...

Descripción completa

Detalles Bibliográficos
Autores principales: van Velzen, Annelies J., Uges, Joris W.F., Heijerman, Harry G.M., Arets, Bert G.M., Nuijsink, Marianne, van der Wiel‐Kooij, Els C., van Maarseveen, Erik M., van Zanten, Gijsbert A., Pullens, Bas, Touw, Daan J., Janssens, Hettie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710527/
https://www.ncbi.nlm.nih.gov/pubmed/31112621
http://dx.doi.org/10.1111/bcp.13988
_version_ 1783446364341927936
author van Velzen, Annelies J.
Uges, Joris W.F.
Heijerman, Harry G.M.
Arets, Bert G.M.
Nuijsink, Marianne
van der Wiel‐Kooij, Els C.
van Maarseveen, Erik M.
van Zanten, Gijsbert A.
Pullens, Bas
Touw, Daan J.
Janssens, Hettie M.
author_facet van Velzen, Annelies J.
Uges, Joris W.F.
Heijerman, Harry G.M.
Arets, Bert G.M.
Nuijsink, Marianne
van der Wiel‐Kooij, Els C.
van Maarseveen, Erik M.
van Zanten, Gijsbert A.
Pullens, Bas
Touw, Daan J.
Janssens, Hettie M.
author_sort van Velzen, Annelies J.
collection PubMed
description AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). 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‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. RESULTS: 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‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb. CONCLUSIONS: Nebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury.
format Online
Article
Text
id pubmed-6710527
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-67105272019-08-28 Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study van Velzen, Annelies J. Uges, Joris W.F. Heijerman, Harry G.M. Arets, Bert G.M. Nuijsink, Marianne van der Wiel‐Kooij, Els C. van Maarseveen, Erik M. van Zanten, Gijsbert A. Pullens, Bas Touw, Daan J. Janssens, Hettie M. Br J Clin Pharmacol Original Articles AIMS: We aimed to compare the pharmacokinetics (PK) and safety profile of tobramycin inhalation solution (TIS) using the I‐neb device to the standard PARI‐LC Plus nebulizer in children with cystic fibrosis. METHODS: A randomized, open‐label, crossover study was performed. In 2 separate study visits, blood samples from 22 children were collected following TIS nebulization with I‐neb (75 mg) and PARI‐LC Plus (300 mg). 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‐1 and NAG) were measured. Patient and nebulizer satisfaction were assessed. RESULTS: 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‐induced subclinical tubular kidney injury. Nebulization time was 50% shorter and patient satisfaction was significantly higher with the I‐neb. CONCLUSIONS: Nebulization of 75 mg TIS with the I‐neb in children with cystic fibrosis resulted in comparable systemic exposure to 300 mg TIS with the PARI‐LC Plus and was well tolerated and preferred over the PARI‐LC Plus. Long‐term safety of TIS nebulization should be monitored clinically, especially regarding the effects on tubular kidney injury. John Wiley and Sons Inc. 2019-07-10 2019-09 /pmc/articles/PMC6710527/ /pubmed/31112621 http://dx.doi.org/10.1111/bcp.13988 Text en © 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
van Velzen, Annelies J.
Uges, Joris W.F.
Heijerman, Harry G.M.
Arets, Bert G.M.
Nuijsink, Marianne
van der Wiel‐Kooij, Els C.
van Maarseveen, Erik M.
van Zanten, Gijsbert A.
Pullens, Bas
Touw, Daan J.
Janssens, Hettie M.
Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
title Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
title_full Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
title_fullStr Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
title_full_unstemmed Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
title_short Pharmacokinetics and safety of tobramycin nebulization with the I‐neb and PARI‐LC Plus in children with cystic fibrosis: A randomized, crossover study
title_sort pharmacokinetics and safety of tobramycin nebulization with the i‐neb and pari‐lc plus in children with cystic fibrosis: a randomized, crossover study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710527/
https://www.ncbi.nlm.nih.gov/pubmed/31112621
http://dx.doi.org/10.1111/bcp.13988
work_keys_str_mv AT vanvelzenanneliesj pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT ugesjoriswf pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT heijermanharrygm pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT aretsbertgm pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT nuijsinkmarianne pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT vanderwielkooijelsc pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT vanmaarseveenerikm pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT vanzantengijsberta pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT pullensbas pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT touwdaanj pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy
AT janssenshettiem pharmacokineticsandsafetyoftobramycinnebulizationwiththeinebandparilcplusinchildrenwithcysticfibrosisarandomizedcrossoverstudy