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.

CompoundApplicationTypeOral or IVSimulated genotype specified?ClearanceaVerificationbPopulation matched?cAcceptance CriteriadSoftwareCitation
AlprazolamDDIFullOralNoIn vitroEN.S.5Winnonlin(Guo et al., 2013)
ClopidogrelDDIMinimalOralYesIn vitroB, ESex1Simcyp(Tornio et al., 2014)
ClopidogrelGeneticsFullOralYesIn vitroB, D, EN.S.1Simcyp(Djebli et al., 2015)
LansoprazoleAbsorptionMinimalOralNoIn vivoCN.S.1Gastroplus(Wu et al., 2013)
MetforminOther (diabetes)FullOralNoin vivoDN.S.3Winnonlin(Li et al., 2015)
MetforminPregnancyFullOralNoIn vivoDSex5Gastroplus(Xia et al., 2013a)
MethadonePregnancyFullOralNoBCB, DSex4Simcyp, Matlab(Ke et al., 2013a)
NisoldipineOther (diabetes)FullOralNoIn vivoDN.S.3Winnonlin(Li et al., 2015)
OseltamivirPediatricsFullBothNoIn vitro, SFC, D, EN.S.1Gastroplus(Parrott et al., 2011)
OseltamivirClinical PKFullOralYesIn vitroDN.S.1PK-Sim(Hu et al., 2014)
OseltamivirRIFullOralNoIn vivoBN.S.1Simcyp(Hsu et al., 2014)
PhenobarbitalDDIFullOralNoIn vivoB,EN.S5WinNonlin(Guo et al., 2013)
PravastatinClinical PKFullIVNoIn vitro, SFCN.S.1Berkeley Madonna(Jones et al., 2012)
PropranololFormulationFullOralNoIn vivoB, CN.S.1Gastroplus(Wang et al., 2013b)
RosuvastatinClinical PKFullIVNoIn vitro, SFCN.S.1Berkeley Madonna(Jones et al., 2012)
SertralineDDIMinimalOralYesIn vitroEN.S.1Simcyp(Siccardi et al., 2013)
TheophyllineDDIMinimalOralNoIn vivoB,EAge, Sex, PGX3Simcyp(Xu et al., 2009)
ValsartanClinical PKFullIVNoIn vitro, SFCN.S.1Berkeley Madonna(Jones et al., 2012)
VerapamilDDIFullOralNoIn vitroEN.S.3Winnonlin(Guo et al., 2013)
VoriconazolePediatricsFullBothNoIn vitro, SFC, DN.S.1Simcyp(Zane and Thakker, 2014)
VoriconazoleDDIMinimalOralYesIn vitroESex, PGX1Simcyp(Damle et al., 2011)
  • a BC = back calculated from in vivo data, SF = scaling factor.

  • b Data sets used in model verification included: (A) Single dose PK, (B) alternative dosing regimen, (C) alternative formulation, (D) alternative population, (E) DDI.

  • c PGX = genotype, N.S. = not specified.

  • 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.