Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation

Salar-Behzadi, Sharareh; Wu, Shengqian; Mercuri, Annalisa; Meindl, Claudia; Stranzinger, Sandra; Frőhlich, Eleonore

doi:10.1016/j.ijpharm.2017.08.124

Cited by 20 publications

(13 citation statements)

References 26 publications

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“…Only a few studies have used the Pulmonary Compartmental Absorption & Transit (PCAT) model in Gastroplus to model absorption from OIDPs . The effect of different carrier properties on systemic PK was investigated by Wu et al .…”

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

“…Only a few studies have used the Pulmonary Compartmental Absorption & Transit (PCAT) model in Gastroplus to model absorption from OIDPs. 70,[81][82][83] The effect of different carrier properties on systemic PK was investigated by Wu et al 81 who measured APSD from two formulations of albuterol sulfate using the Cyclocaps capsules Teva UK, Harlow, UK in an Aerolizer device, where glass beads were used as carrier particles as opposed to lactose because of the ease of surface modification. Values of maximum plasma concentration (C max ) and FPF were increased by factors of 1.20 and 1.36, respectively, for the formulation where the glass bead surface was modified as opposed to the formulation with the unmodified glass beads.…”

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

“…Values of maximum plasma concentration (C max ) and FPF were increased by factors of 1.20 and 1.36, respectively, for the formulation where the glass bead surface was modified as opposed to the formulation with the unmodified glass beads. 81 The predictive power of deposition and permeability estimates provided by the Gastroplus PCAT model when compared with in vivo deposition data and experimentally determined alveolar permeability data was tested by Salar-Behzadi et al, 82 where predictions of C max and area under the time-concentration curve from time 0 to time t from Turbuhaler (budesonide DPI) when compared with available PK data were greatly improved by the addition of experimental data. Bäckman et al 83 used Gastroplus PCAT to model the exposure of a poorly soluble investigational compound, AZD5423, using a number of delivery methods, including different nebulizers and DPI devices, where it was found that total lung deposition values from an in vitro model were not alone predictive of differences in PK metrics, but when deposition pattern and dissolution were also considered, the predictions matched well with available PK data.…”

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

“…If PK data from an intravenously administered drug are available, this can be useful for predicting clearance parameters. Wu et al 81 , Salar-Behzadi et al, 82 and Bäckman et al 83 used intravenous data to estimate clearance, whereas others did not, presumably because they were unavailable. 70,84 Some studies used data from an oral dosage form of the same drug to build an oral model with the purpose of increasing confidence in the lung model.…”

Section: Model Credibility-verification and Validationmentioning

confidence: 99%

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In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

Walenga

Babiskin

Zhao

2019

CPT Pharmacom & Syst Pharma

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The development of generic, single‐entity, drug–device combination products for orally inhaled drug products is challenging in part because of the complex nature of device design characteristics and the difficulties associated with establishing bioequivalence for a locally acting drug product delivered to the site of action in the lung. This review examines in silico models that may be used to support the development of generic orally inhaled drug products and how model credibility may be assessed.

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Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

Section: Pbpk Modeling Coupled With Cfd To Predict Drug Absorption Inmentioning

confidence: 99%

Section: Model Credibility-verification and Validationmentioning

confidence: 99%

See 3 more Smart Citations

In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

Walenga

Babiskin

Zhao

2019

CPT Pharmacom & Syst Pharma

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Organotypic Models of Lung Cancer

Pomerenke

2017

Current Topics in Microbiology and Immunology

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Human lung cancer is one of the leading causes of death worldwide, with nearly 2 million of new cases diagnosed each year, often too late for a successful therapeutic intervention. In this chapter, organotypic models of lung cancer will be reviewed. Ex vivo tissue explants, spheroids, organoids, and novel bioengineering approaches are currently being used to study human lung cancer. Although there is no ideal method that will fully recapitulate the complex human lung architecture, the three-dimensional (3D) organotypic models described here represent a major advance from classical two-dimensional (2D) tissue culture models. Organotypic tissue cultures are better at predicting in vivo tissue responses to anticancer drugs or carcinogenic toxins. In addition, there is also a possibility to use these systems as part of personalized medicine (e.g., to assist clinicians in selecting appropriate therapeutic choices based on individual patient-derived tissue responses to drugs in vitro). There is still a need for improvement in the 3D culture systems, such as automation for high-throughput testing and reduction of costs. However, given the large number of failed clinical trials due to safety or efficacy reasons, more attention should be given to these more physiologically relevant 3D organotypic tissue culture models.

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Physiologically Based Pharmacokinetic Modelling of Inhaled Nemiralisib: Mechanistic Components for Pulmonary Absorption, Systemic Distribution, and Oral Absorption

et al. 2021

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Background and Objectives Physiologically based pharmacokinetic (PBPK) modelling has evolved to accommodate different routes of drug administration and enables prediction of drug concentrations in tissues as well as plasma. The inhalation route of administration has proven successful in treating respiratory diseases but can also be used for rapid systemic delivery, holding great promise for treatment of diseases requiring systemic exposure. The objective of this work was to develop a PBPK model that predicts plasma and tissue concentrations following inhalation administration of the PI3Kδ inhibitor nemiralisib. Methods A PBPK model was built in GastroPlus ® that includes a complete mechanistic description of pulmonary absorption, systemic distribution and oral absorption following inhalation administration of nemiralisib. The availability of clinical data obtained after intravenous, oral and inhalation administration enabled validation of the model with observed data and accurate assessment of pulmonary drug absorption. The PBPK model described in this study incorporates novel use of key parameters such as lung systemic absorption rate constants derived from human physiological lung blood flows, and implementation of the specific permeability-surface area product per millilitre of tissue cell volume (SpecPStc) to predict tissue distribution. Results The inhaled PBPK model was verified using plasma and bronchoalveolar lavage fluid concentration data obtained in human subjects. Prediction of tissue concentrations using the permeability-limited systemic disposition tissue model was further validated using tissue concentration data obtained in the rat following intravenous infusion administration to steady state. Conclusions Fully mechanistic inhaled PBPK models such as the model described herein could be applied for cross molecule assessments with respect to lung retention and systemic exposure, both in terms of pharmacology and toxicology, and may facilitate clinical indication selection.

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Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation

Cited by 20 publications

References 26 publications

In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

Organotypic Models of Lung Cancer

Physiologically Based Pharmacokinetic Modelling of Inhaled Nemiralisib: Mechanistic Components for Pulmonary Absorption, Systemic Distribution, and Oral Absorption

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