Table 6.
Summary of the PBPK models published for compounds that are FDA probe substrates, inhibitors, or inducers but the models were developed for a different purpose than the FDA category.
| Compound | Application | Type | Oral or IV | Simulated genotype specified? | Clearancea | Verificationb | Population matched?c | Acceptance Criteriad | Software | Citation |
|---|---|---|---|---|---|---|---|---|---|---|
| Alprazolam | DDI | Full | Oral | No | In vitro | E | N.S. | 5 | Winnonlin | (Guo et al., 2013) |
| Clopidogrel | DDI | Minimal | Oral | Yes | In vitro | B, E | Sex | 1 | Simcyp | (Tornio et al., 2014) |
| Clopidogrel | Genetics | Full | Oral | Yes | In vitro | B, D, E | N.S. | 1 | Simcyp | (Djebli et al., 2015) |
| Lansoprazole | Absorption | Minimal | Oral | No | In vivo | C | N.S. | 1 | Gastroplus | (Wu et al., 2013) |
| Metformin | Other (diabetes) | Full | Oral | No | in vivo | D | N.S. | 3 | Winnonlin | (Li et al., 2015) |
| Metformin | Pregnancy | Full | Oral | No | In vivo | D | Sex | 5 | Gastroplus | (Xia et al., 2013a) |
| Methadone | Pregnancy | Full | Oral | No | BC | B, D | Sex | 4 | Simcyp, Matlab | (Ke et al., 2013a) |
| Nisoldipine | Other (diabetes) | Full | Oral | No | In vivo | D | N.S. | 3 | Winnonlin | (Li et al., 2015) |
| Oseltamivir | Pediatrics | Full | Both | No | In vitro, SF | C, D, E | N.S. | 1 | Gastroplus | (Parrott et al., 2011) |
| Oseltamivir | Clinical PK | Full | Oral | Yes | In vitro | D | N.S. | 1 | PK-Sim | (Hu et al., 2014) |
| Oseltamivir | RI | Full | Oral | No | In vivo | B | N.S. | 1 | Simcyp | (Hsu et al., 2014) |
| Phenobarbital | DDI | Full | Oral | No | In vivo | B,E | N.S | 5 | WinNonlin | (Guo et al., 2013) |
| Pravastatin | Clinical PK | Full | IV | No | In vitro, SF | C | N.S. | 1 | Berkeley Madonna | (Jones et al., 2012) |
| Propranolol | Formulation | Full | Oral | No | In vivo | B, C | N.S. | 1 | Gastroplus | (Wang et al., 2013b) |
| Rosuvastatin | Clinical PK | Full | IV | No | In vitro, SF | C | N.S. | 1 | Berkeley Madonna | (Jones et al., 2012) |
| Sertraline | DDI | Minimal | Oral | Yes | In vitro | E | N.S. | 1 | Simcyp | (Siccardi et al., 2013) |
| Theophylline | DDI | Minimal | Oral | No | In vivo | B,E | Age, Sex, PGX | 3 | Simcyp | (Xu et al., 2009) |
| Valsartan | Clinical PK | Full | IV | No | In vitro, SF | C | N.S. | 1 | Berkeley Madonna | (Jones et al., 2012) |
| Verapamil | DDI | Full | Oral | No | In vitro | E | N.S. | 3 | Winnonlin | (Guo et al., 2013) |
| Voriconazole | Pediatrics | Full | Both | No | In vitro, SF | C, D | N.S. | 1 | Simcyp | (Zane and Thakker, 2014) |
| Voriconazole | DDI | Minimal | Oral | Yes | In vitro | E | Sex, PGX | 1 | Simcyp | (Damle et al., 2011) |
BC = back calculated from in vivo data, SF = scaling factor.
Data sets used in model verification included: (A) Single dose PK, (B) alternative dosing regimen, (C) alternative formulation, (D) alternative population, (E) DDI.
PGX = genotype, N.S. = not specified.
Acceptance criteria fell into 5 categories: (1) Not specified, (2) Ratio of PK parameter(s) must be within 30% of observed ratio, (3) Ratio of PK parameter(s) must be within 2 fold of observed ratio, (4) PK parameters must be within 30% of observed parameters, (5) PK parameters must be within 2 fold of observed parameters.