Table 4

PBPK models published for P450 inducers

Enzyme InducedCompoundApplicationMinimal or FullIV or OralClearanceaSimulated genotype specified?Population matched?bVerificationcAcceptance CriteriadSoftwareCitation
CYP2B6 and CYP3A4EfavirenzDDIMinimalOralIn vitroYesN.SA, E1Simcyp(Siccardi et al., 2013)
EfavirenzAbsorptionFullOralIn vitroNoN.S.B5Matlab(Rajoli et al., 2014)
EfavirenzDDIFullOralIn vitroYesSexD, E1Simcyp(Rekic et al., 2011)
CYP3A4CarbamazepineDDIFullOralIn vitroNoN.S.B, E5WinNonlin(Guo et al., 2013)
EtravirineAbsorptionFullOralIn vitroNoN.S.B5Matlab(Rajoli et al., 2014)
RifampinDDIFullOralBCNoN.S.E5Gastroplus(Baneyx et al., 2014)
RifampinDDIFullOralIn vivoNoN.S.B, E5WinNonlin(Guo et al., 2013)
RifampinDDIFullOralBCNoAge, sex, PGXA1Simcyp(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.