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Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution
Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624821/ https://www.ncbi.nlm.nih.gov/pubmed/26316105 http://dx.doi.org/10.1007/s10928-015-9438-9 |
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author | Clewe, Oskar Karlsson, Mats O. Simonsson, Ulrika S. H. |
author_facet | Clewe, Oskar Karlsson, Mats O. Simonsson, Ulrika S. H. |
author_sort | Clewe, Oskar |
collection | PubMed |
description | Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10928-015-9438-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4624821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-46248212015-11-03 Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution Clewe, Oskar Karlsson, Mats O. Simonsson, Ulrika S. H. J Pharmacokinet Pharmacodyn Original Paper Bronchoalveolar lavage (BAL) is a pulmonary sampling technique for characterization of drug concentrations in epithelial lining fluid and alveolar cells. Two hypothetical drugs with different pulmonary distribution rates (fast and slow) were considered. An optimized BAL sampling design was generated assuming no previous information regarding the pulmonary distribution (rate and extent) and with a maximum of two samples per subject. Simulations were performed to evaluate the impact of the number of samples per subject (1 or 2) and the sample size on the relative bias and relative root mean square error of the parameter estimates (rate and extent of pulmonary distribution). The optimized BAL sampling design depends on a characterized plasma concentration time profile, a population plasma pharmacokinetic model, the limit of quantification (LOQ) of the BAL method and involves only two BAL sample time points, one early and one late. The early sample should be taken as early as possible, where concentrations in the BAL fluid ≥ LOQ. The second sample should be taken at a time point in the declining part of the plasma curve, where the plasma concentration is equivalent to the plasma concentration in the early sample. Using a previously described general pulmonary distribution model linked to a plasma population pharmacokinetic model, simulated data using the final BAL sampling design enabled characterization of both the rate and extent of pulmonary distribution. The optimized BAL sampling design enables characterization of both the rate and extent of the pulmonary distribution for both fast and slowly equilibrating drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10928-015-9438-9) contains supplementary material, which is available to authorized users. Springer US 2015-08-28 2015 /pmc/articles/PMC4624821/ /pubmed/26316105 http://dx.doi.org/10.1007/s10928-015-9438-9 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Paper Clewe, Oskar Karlsson, Mats O. Simonsson, Ulrika S. H. Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
title | Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
title_full | Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
title_fullStr | Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
title_full_unstemmed | Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
title_short | Evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
title_sort | evaluation of optimized bronchoalveolar lavage sampling designs for characterization of pulmonary drug distribution |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624821/ https://www.ncbi.nlm.nih.gov/pubmed/26316105 http://dx.doi.org/10.1007/s10928-015-9438-9 |
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