Successful examples of proteomics informed PBPK modeling and IVIVE for predicting drug disposition

DrugsEnzymes and/or Transporters InvolvedStudy ObjectiveStudy PopulationPredictive Accuracy (P/O fold ratio)Software UsedReferences
ZidovudineUGT2B7Liver cirrhosisAdult Child Pugh C subjects0.97
Prasad et al., 2018
Age-dependent PKNeonates, infants and children0.52*Bhatt et al., 2019
MorphineUGT2B7 and OCT1Liver cirrhosisAdult Child Pugh C subjects0.97SimcypPrasad et al., 2018
Age-dependent PKNeonates, infants and children0.52*Prasad et al., 2018
AcetaminophenSULT1A1/1A3/1B1/2A1Age-dependent PK and its effect on fraction of drug metabolizedNeonates and infants0.98GastroPlusLadumor et al., 2019a
RosuvastatinOATP1B1/1B3/2B1, NTCPEffect of body weight on rosuvastatin PKAdult healthy subjects with varying body weights0.95Semimechanistic model using RWegler et al., 2021
LamotrigineUGT1A3/1A4/2B7Alcoholic cirrhosisAdult hepatic impaired subjects0.83GastroPlusLadumor et al., 2019b
OseltamivirCES1/2Age-dependent PKInfants0.52.1*SimcypBoberg et al., 2017
EthionamideFMO3Drug-drug interaction with methimazole and impact of genetic polymorphismHealthy subjects0.62.6*Simcyp
Nguyen et al., 2019
Dexamethasone, betamethasone, darunavir, and lopinavirP-gpMaternal-fetal PKNonpregnant (control) and pregnant population0.81.25SimcypAnoshchenko et al., 2021
DigoxinOATP4C1Moderate and severe renal impairmentRenal impaired population0.52SimcypScotcher et al., 2017
Cidofovir, oseltamivir, carboxylate and cefuroximeOATSevere renal impairmentRenal impaired population0.52SimcypHsu et al., 2014
Adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir, carboxylate and sitagliptinOATModerate and severe renal impairmentRenal impaired population0.671.5SimcypHsueh et al., 2018
  • *Range (multiple doses and route of administration were tested).