Article Figures & Data
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Data Supplement
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Supplemental Method
Table S1. Algebraic expressions for aerodynamic filtration efficiency in the ICRP 66 deposition model (ICRP, 1995).
Table S2. Algebraic expressions for thermodynamic filtration efficiency in the ICRP 66 deposition model (ICRP, 1995).
Table S3. Algebraic expressions for a volumetric fraction in the ICRP 66 deposition model (ICRP, 1995).
Table S4. Respiratory tissue-specific input parameters for the OI-PBPK model (ICRP, 1995; Patton and Byron, 2007).
Table S5. Summary of system-dependent parameters for the reference adult male (Valentin, 2002)*
Table S6. Summary of input parameters for the morphine OI-PBPK model.
Table S7. Summary of input parameters for the nicotine OI-PBPK model.
Table S8. Input and output for predicting the DE of morphine (administered via a nebulizer) in each region of the respiratory tract using the ICRP 66 deposition model.
Table S9. Input and output for predicting the DE of nicotine (administered via cigarette smoking) in each region of the respiratory tract using the ICRP 66 deposition model.
Table S10. Summary of input parameters for morphine and nicotine OI model.
Table S11. Comparison of simulated and observed PK parameters of morphine after IV infusion (IV Inf) or oral inhalation (OI; nebulizer)
Table S12. Comparison of the simulated and observed PK parameters of nicotine after IV infusion.
Table S13. Comparison of the simulated and observed PK parameters of nicotine after oral inhalation (cigarett smoking) when fhyg and DFscalar were incorporated.
Fig. S1. Sensitivity analyses to demonstrate the impact of change in inhalation flow (a1 and a2), inhalation volume (V; b1 and b2), and hygroscopic growth factor (fhyg; c1 and c2)) on total and regional respiratory tract deposition, as well as pharmacokinetic (PK) endpoints of drug X. ET2, extrathoracic (oral passage); BB, bronchial; bb, bronchiolar; AL, Alveolar; C, central region (BB+bb); P, peripheral region (AL).
Fig. S2. Sensitivity analyses to demonstrate the impact of epithelial membrane transport on systemic and local epithelial concentrations of drug Y in various regions of the respiratory tract (ET2, BB, bb and AL) in the presence of a) apical influx transport (clearance: 0 L/h, purple color; 0.0001 L/h, green color; 0.0005 L/h, sky blue color); or b) apical efflux transport (clearance: 0 L/h, purple color; 50 L/h, green color; 250 L/h, sky blue color).
Fig. S3. Sensitivity analyses to demonstrate the impact of apical subepithelial membrane (or basal epithelial membrane) transport on systemic and local subepithelial concentrations of drug Y in various respiratory tract compartments (ET2, BB, bb and AL) in the presence of a) influx transport (clearance: 0 L/h, purple color; 50 L/h, green color; 250 L/h, sky blue color); or b) efflux transport (clearance: 0 L/h, purple color; 10 L/h, green color; 50 L/h, sky blue color).
Fig. S4. Sensitivity analyses to demonstrate the impact of epithelial metabolism on systemic and local epithelial concentrations of drug Y in various lung compartments (ET2, BB, bb and AL) in the presence of metabolism (clearance: 0 L/h, purple color; 10 L/h, green color; 50 L/h, sky blue color).
Fig. S5. Sensitivity analyses to demonstrate the impact of tissue retention on systemic and local epithelial concentrations of drug Y in various respiratory tract compartments (ET2, BB, bb and AL) in the presence of tissue retention (dissociation rate constant: 10 1/h, purple color; 50 1/h, green color; 250 1/h, sky blue color; in all these cases, the association rate constant and fatty acid concentrations were fixed to 50 L/mg/h and 10.0 mg/L).
Fig. S6. Sensitivity analyses to demonstrate the impact of dissolution rate (z-factor) on systemic and local epithelial concentrations of drug X in various respiratory tract compartments (ET2, BB, bb and AL) in the presence of dissolution rate (z-factor 0.01 L/mg/h, purple color; 0.001 L/mg/h, green color; 0.0001 L/mg/h, sky blue color).
Supplemental References
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