Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling

AIMS: Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of this article is: (1) to study the PK characterist...

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Autores principales: Zhang, Jisheng, Wu, Keheng, Liu, Bo, Hou, Shuguang, Li, Xue, Ye, Xiang, Liu, Jack, He, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941642/
https://www.ncbi.nlm.nih.gov/pubmed/36824609
http://dx.doi.org/10.3389/fmed.2023.1056318
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author Zhang, Jisheng
Wu, Keheng
Liu, Bo
Hou, Shuguang
Li, Xue
Ye, Xiang
Liu, Jack
He, Qing
author_facet Zhang, Jisheng
Wu, Keheng
Liu, Bo
Hou, Shuguang
Li, Xue
Ye, Xiang
Liu, Jack
He, Qing
author_sort Zhang, Jisheng
collection PubMed
description AIMS: Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of this article is: (1) to study the PK characteristics and bioequivalence of ipratropium bromide (IB) inhalation aerosol, reference and test products in healthy Chinese subjects; (2) to establish a physiologically based pharmacokinetic (PBPK) model and verify the accuracy of the model in predicting bioequivalence; (3) attempt to use the model to predict the regional distribution of particles in the lung after inhalation, and discuss the effect of gastrointestinal drug absorption of IB on systemic exposure. METHODS: The study involved two clinical studies. Clinical study-1 (registration number: CTR20201284) was used with non-clinical data to construct and validate a PBPK model in the B(2)O simulator, a web-based virtual drug development platform. This model assessed different test and reference products’ bioequivalence. Results were compared to a second clinical study (Clinical study-2: registration number CTR20202291). The particles’ regional distribution in the lung and the gastrointestinal absorption effect on systemic exposure were discussed based on the simulation results. RESULTS: The established PBPK model successfully simulated the in vivo PK characteristics of IB inhalation aerosol, with r(2) close to 1. Gastrointestinal absorption had a negligible effect on systemic exposure. Particles accumulated in the alveolar area were cleared within an hour, followed by particles in the bronchioles and bronchi. CONCLUSION: This model provided a reliable method for exploring the correlation between in vitro and in vivo PK studies of IB inhalation aerosols. According to the simulation results, the test and reference products were bioequivalent.
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spelling pubmed-99416422023-02-22 Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling Zhang, Jisheng Wu, Keheng Liu, Bo Hou, Shuguang Li, Xue Ye, Xiang Liu, Jack He, Qing Front Med (Lausanne) Medicine AIMS: Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of this article is: (1) to study the PK characteristics and bioequivalence of ipratropium bromide (IB) inhalation aerosol, reference and test products in healthy Chinese subjects; (2) to establish a physiologically based pharmacokinetic (PBPK) model and verify the accuracy of the model in predicting bioequivalence; (3) attempt to use the model to predict the regional distribution of particles in the lung after inhalation, and discuss the effect of gastrointestinal drug absorption of IB on systemic exposure. METHODS: The study involved two clinical studies. Clinical study-1 (registration number: CTR20201284) was used with non-clinical data to construct and validate a PBPK model in the B(2)O simulator, a web-based virtual drug development platform. This model assessed different test and reference products’ bioequivalence. Results were compared to a second clinical study (Clinical study-2: registration number CTR20202291). The particles’ regional distribution in the lung and the gastrointestinal absorption effect on systemic exposure were discussed based on the simulation results. RESULTS: The established PBPK model successfully simulated the in vivo PK characteristics of IB inhalation aerosol, with r(2) close to 1. Gastrointestinal absorption had a negligible effect on systemic exposure. Particles accumulated in the alveolar area were cleared within an hour, followed by particles in the bronchioles and bronchi. CONCLUSION: This model provided a reliable method for exploring the correlation between in vitro and in vivo PK studies of IB inhalation aerosols. According to the simulation results, the test and reference products were bioequivalent. Frontiers Media S.A. 2023-02-07 /pmc/articles/PMC9941642/ /pubmed/36824609 http://dx.doi.org/10.3389/fmed.2023.1056318 Text en Copyright © 2023 Zhang, Wu, Liu, Hou, Li, Ye, Liu and He. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Zhang, Jisheng
Wu, Keheng
Liu, Bo
Hou, Shuguang
Li, Xue
Ye, Xiang
Liu, Jack
He, Qing
Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling
title Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling
title_full Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling
title_fullStr Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling
title_full_unstemmed Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling
title_short Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling
title_sort bioequivalence study of ipratropium bromide inhalation aerosol using pbpk modelling
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941642/
https://www.ncbi.nlm.nih.gov/pubmed/36824609
http://dx.doi.org/10.3389/fmed.2023.1056318
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