This contribution contains the MoBi implementation of a mechanistic physiologically-based pharmacokinetic inhalation model that brings together lung anatomy, particle deposition, particle dissolution, and mucociliary clearance from previous work and connects it to a two-compartment model.
In this model, the lung is separated into the extrathoracic region and 24 lung generations (or sections) that each consist of concentric layers: epithelial lining fluid, epithelium, and subepithelium. The model allows for absorption of particles in the lung as well as oral absorption of particles in the extrathoracic region.
Using MoBi and the ospsuite R package, the user enters parameters describing the physicochemical properties of the molecule, the micro-constants pertaining to the two-compartment model, oral and lung bioavailabilities, particle size distribution, and dose.
Simulation of the model returns:
- amount or concentration of drug at each compartment and at each generation of the lung over the time of the simulation,
- amount or concentration of drug at each compartment of the two-compartment model as well as the extrathoracic region.
| File name | Description |
|---|---|
| Inhalation_model_user_guide.pdf | Includes: 1. Introduction to the model and model details 2. A description of the model implementation in Mobi 3. Step-by-step tutorial of a basic inhalation simulation |
| Inhalation_model_structure_evaluation.pdf | Slide deck demonstrating the use of the inhalation model to capture the observed behaviour of four molecules of varying solubilities. |
| inhalation_model_two_compt_1_bin.mbp3 | MoBi project template containing the inhalation model connected to a two-compartment model |
| populate_model.R | R script that is used to calculate deposition fractions based on empirical equations (Yu & Diu, 1982) |
| custom_deposition.R | R script that is used to specify the deposition fractions directly |
| configure_inhalation_parameters.R | Template to guide the use of the populate_model.R and custom_deposition.R files. It is currently configured for the ciprofloxacin which is used in the tutorial within the user guide |
| ParticleBin_1.pkml | Template for a single particle bin. This file can be used to add additional particle bins in the case of a polydisperse formulation |
| Standard_Molecule.pkml | Template for a generic molecule building block. This file is used to load the parameter "Solubility in epithelial lining fluid" |
| stass_2017_ciprofloxacin_inhaled.pkml | Building block that contains Stass et al (2017) data used in the tutorial within the user guide |
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