TABLE 2.
Comparison of AUC parameters of peripheral compartment in PBPK, lumped, and compartment models for 20 compounds.
| Model | PBPK model | Lumped model | Compartment model |
|---|---|---|---|
| Tissue, compartment | Adipose, bone, brain, muscle, skin, heart, rest of body | Non-eliminating tissues compartment (NET) | Peripheral compartment |
| Parameter (unit) | Average of tissue AUClast (mg•h/L) (2-fold range) | AUClast at NET (mg•h/L) (2-fold range) | AUClast at peripheral compartment (mg•h/L) (2-fold range) |
| Compound | |||
| Alfentanil | 1.772 (0.886-3.544) | 0.994 (0.497-1.987) | - |
| Amlodipine | 9.979 (4.989-19.957) | 11.920 (5.960-23.840) | - |
| Artemether | 27.217 (13.609-54.435) | 19.090 (9.545-38.180) | - |
| Caffeine | 0.901 (0.450-1.801) | 0.638 (0.319-1.276) | - |
| Clozapine | 142.308 (71.154-284.617) | 134.485 (67.242-268.969) | - |
| Cyclosporine A | 17.777 (8.888-35.553) | 12.601 (6.300-25.202) | - |
| Digoxin | 0.077 (0.039-0.154) | 0.057 (0.028-0.113) | 0.030 (0.015-0.059) |
| Fluoxetine | 20.178 (10.089-40.356) | 13.400 (6.700-26.799) | - |
| Metoprolol | 5.476 (2.738-10.952) | 2.644 (1.322-5.288) | - |
| Midazolam | 8.860 (4.430-17.720) | 5.189 (2.594-10.377) | 0.100 (0.050-0.201)+,# |
| Nevirapine | 315.957 (157.979-631.914) | 208.837 (104.418-417,674) | 202.734 (101.367-405.467) |
| Ofloxacin | 34.537 (17.269-69.074) | 29.840 (14.920-59.680) | 55.224 (27.612-110.449) |
| Paracetamol | 18.966 (9.483-37.931) | 19.120 (9.560-38.240) | 68.139 (34.070-136.278)+,# |
| Pioglitazone | 0.348 (0.174-0.696) | 0.312 (0.156-0.624) | 3.002 (1.501-6.005)+,# |
| Rifampicin | 139.803 (69.901-279.605) | 163.653 (81.827-327.307) | - |
| S-Warfarin | 6.697 (3.348-13.394) | 5.905 (2.953-11.810) | - |
| Telmisartan | 164.733 (82.367-329.466) | 123.565 (61.783-247.130) | 0.694 (0.347-1.388)+,# |
| Theophylline | 291.616 (145.808-583.232) | 279.114 (139.557-558.228) | - |
| Thiopental | 11,940.270 (5,970.135-23880.540) | 7,818.454 (3,909.227-15636.908) | 2,773.715 (1,386.858-5,547.430) |
| Voriconazole | 260.225 (130.113-520.450) | 273.008 (136.504-546.016) | 63.054 (31.527-126.108) |
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).