TABLE 1.
Comparison of AUC parameters of central compartment in PBPK, lumped, and compartment models for 20 compounds.
| Model | PBPK model | Lumped model | Compartment model |
|---|---|---|---|
| Tissue, compartment | Lungs, arterial blood, venous blood | Lumped central compartment (LCEN) | Central compartment |
| Parameter (unit) | Average of tissue AUClast (mg•h/L) | AUClast at LCEN (mg•h/L) | AUClast at central compartment (mg•h/L) (2-fold range) |
| Compound | (2-fold range) | (2-fold range) | |
| Alfentanil | 0.348 (0.174-0.697) | 0.351 (0.175-0.702) | 0.585 (0.293-1.171) |
| Amlodipine | 7.598 (3.799-15.195) | 0.505 (0.253-1.011)* | 0.496 (0.248-0.993)# |
| Artemether | 2.608 (1.304-5.216) | 2.877 (1.438-5.754) | 0.173 (0.087-0.346)+,# |
| Caffeine | 1.349 (0.674-2.698) | 1.482 (0.741-2.963) | 0.953 (0.477-1.906) |
| Clozapine | 130.033 (65.017-260.066) | 12.823 (6.411-25.645)* | 14.172 (7.086-28.344)# |
| Cyclosporine A | 21.776 (10.888-43.552) | 12.285 (6.143-24.571) | 18.363 (9.181-36.726) |
| Digoxin | 0.056 (0.028-0.111) | 0.060 (0.030-0.120) | 0.030 (0.015-0.060) |
| Fluoxetine | 2.736 (1.368-5.471) | 1.926 (0.963-3.851) | 4.511 (2.256-9.022) |
| Metoprolol | 0.987 (0.494-1.974) | 1.074 (0.537-2.147) | 0.630 (0.315-1.260) |
| Midazolam | 1.005 (0.503-2.010) | 0.977 (0.489-1.954) | 0.098 (0.049-0.196) |
| Nevirapine | 146.303 (73.151-292.605) | 164.225 (82.113-328.450) | 203.575 (101.787-407.150) |
| Ofloxacin | 50.220 (25.110-100.440) | 53.246 (26.623-106.492) | 55.173 (27.586-110.345) |
| Paracetamol | 28.650 (14.325-57.300) | 33.827 (16.914-67.655) | 67.964 (33.982-135.929) |
| Pioglitazone | 2.368 (1.184-4.735) | 3.201 (1.600-6.402) | 5.529 (2.765-11.058) |
| Rifampicin | 153.468 (76.734-306.937) | 79.553 (39.777-159.106) | 65.084 (32.542-130.168) |
| S-Warfarin | 28.075 (14.037-56.150) | 35.292 (17.646-70.584) | 30.006 (15.003-60.012) |
| Telmisartan | 760.097 (380.049-1,520.195) | 986.822 (493.411-1973.643) | 0.707 (0.353-1.414)+,# |
| Theophylline | 468.329 (234.164-936.658) | 554.051 (277.026-1,108.102) | 65.239 (32.620-130.479) |
| Thiopental | 1,688.083 (844.042-3,376.166) | 1819.869 (909.935-3,639.738) | 3,015.313 (1,507.657-6,030.626) |
| Voriconazole | 43.587 (21.794-87.174) | 46.360 (23.180-92.720) | 63.400 (31.700-126.800) |
AUC, area under the concentration-time curve. *,+, # marks are attached after compound name if the AUC, parameters among PBPK, model, lumped model, and compartment model are significantly different (p < 0.05) (post-hoc analysis: *PBPK, model and lumped model, #PBPK, model and compartment model, +lumped model and compartment model).