Table I.
Typical value parameters for the BUD, FLU, FP, and TA modules of the PK trial simulation tool
| Parameter | Unit | BUDa (DPI) | FLU (MDI) | FPa (DPI) | TAa (MDI) |
|---|---|---|---|---|---|
| θ (F Lung) | 0.3b | 0.24b | 0.16b | 0.15b | |
| θ (F C) | 0.5b, g | 0.5b, g | 0.5b, g | 0.5b, g | |
| θ (F BA) | 0.11 | 0.2 | 0e | 0.23 | |
| θ (k muc) | h−1 | 0.938b (14) | 0.938b (14) | 0.938b (14) | 0.938b (14) |
| θ (k diss) | h−1 | 17.8b | 14b | 0.189f | 1.2b |
| θ (k pul,C) | h−1 | 10c | 10c | 10c | 10c |
| θ (k pul,P) | h−1 | 20c | 20c | 20c | 20c |
| θ (k a) | h−1 | 0.45 (20) | 14 | –e | 0.91 (21,22) |
| θ (CL) | L/h | 85 | 55 | 73 | 39 |
| θ (V C) | L | 100 | 70 | 31 | 154 |
| θ (k 12) | h−1 | 20.01 | 0.41 | 1.78 | –d |
| θ (k 21) | h−1 | 11.06 | 0.82 | 0.09 | –d |
Typical value parameters are based upon a publication by Krishnaswami et al. (18) unless otherwise stated (reference(s) in parenthesis). Further literature references that are related to the selection of the typical value parameters are given as additional references. BSV and WSV terms are set (by default) to values of 20% and 30% (expressed as CV%), respectively, and can be changed by the user
BUD budesonide, FLU flunisolide, FP fluticasone propionate, TA triamcinolone acetonide, DPI dry powder inhaler, MDI metered-dose inhaler
aAdditional references: BUD (23–29), FP (30–33), and TA (34)
bParameters are set to literature estimates but can be changed by user. The default values for θ (F Lung) represent specific values for the inhalers (i.e., BUD (Turbohaler), FLU (MDI), FP (Diskus), and TA (MDI))
cParameters are arbitrarily chosen to represent fast absorption of dissolved lipophilic substances and to account for possible faster absorption from peripheral lung regions and can be changed by the user
dOne compartment body model seems to be more suitable to describe PK of TA
eThe oral bioavailability of FP is <1% and negligible for the plasma concentration time profile
fThe dissolution rate constant (k diss) for the FP module is based upon unpublished in vitro dissolution data and PK analysis of unpublished FP data
gLiterature estimates for F C (i.e. central vs. peripheral lung (C/P) deposition ratio) ratio for the different formulations are either not available or not applicable for the model (see Discussion). Thus, an educated guess of 0.5 (i.e., C/P deposition ratio of 1) was used as a default value for the modules