Table 4.
PBPK models published for P450 inducers
| Enzyme Induced | Compound | Application | Minimal or Full | IV or Oral | Clearancea | Simulated genotype specified? | Population matched?b | Verificationc | Acceptance Criteriad | Software | Citation |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CYP2B6 and CYP3A4 | Efavirenz | DDI | Minimal | Oral | In vitro | Yes | N.S | A, E | 1 | Simcyp | (Siccardi et al., 2013) |
| Efavirenz | Absorption | Full | Oral | In vitro | No | N.S. | B | 5 | Matlab | (Rajoli et al., 2014) | |
| Efavirenz | DDI | Full | Oral | In vitro | Yes | Sex | D, E | 1 | Simcyp | (Rekic et al., 2011) | |
| CYP3A4 | Carbamazepine | DDI | Full | Oral | In vitro | No | N.S. | B, E | 5 | WinNonlin | (Guo et al., 2013) |
| Etravirine | Absorption | Full | Oral | In vitro | No | N.S. | B | 5 | Matlab | (Rajoli et al., 2014) | |
| Rifampin | DDI | Full | Oral | BC | No | N.S. | E | 5 | Gastroplus | (Baneyx et al., 2014) | |
| Rifampin | DDI | Full | Oral | In vivo | No | N.S. | B, E | 5 | WinNonlin | (Guo et al., 2013) | |
| Rifampin | DDI | Full | Oral | BC | No | Age, sex, PGX | A | 1 | Simcyp | (Neuhoff et al., 2013b) |
a
BC = back calculated from in vivo data.
b
PGX = genotype, N.S. = not specified.
c
Data sets used in model verification included: (A) Single dose PK, (B) alternative dosing regimen, (C) alternative formulation, (D) alternative population, (E) DDI.
d
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.