Search the PBPK Model Repository

Quickly find freely available drug and population models in our PBPK model repository.

The models provided have been collated from published examples which authors have shared in our Published Model Collection or developed as part of various global health projects in our Global Health Collection. This search facility searches both model collections simultaneously.

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Found 108 Matches

Darunavir
Model Files Publication

Brand Name(s) include: Prezista, Prezcobix, Rezolsta

Disease: HIV

Drug Class: Antiretroviral

Date of Review: 2020

Number of Models Reviewed: 2

Number of Models added to the Repository: 2

The model at-a-glance

Publication – MODEL 1

Wagner et al., Physiologically-Based Pharmacokinetic Modeling for Predicting the Effect of Intrinsic and Extrinsic Factors on Darunavir or Lopinavir Exposure Co-administered with Ritonavir. J Clin Pharmacol. 2017 October ; 57(10): 1295–1304.  (FDA model)

 Simcyp Version

V13

 Published Model Application

Prediction of exposure in hepatic impairment

 Absorption Model
  • First-Order
 Volume of Distribution Details
  • Minimal

 Route of Elimination
  • CYP3A4, Non-specific metabolism, renal clearance
  • Bottom-up approach for clearance, fm,CYP3A4 was optimized with clinical DDI data with ketoconazole

 Perpetrator DDI
  • CYP2B6 Competitive Inhibitor
  • CYP2C9 Competitive Inhibitor
  • CYP2C19 Competitive Inhibitor
  • CYP2D6 Competitive Inhibitor
  • CYP3A4 Competitive Inhibitor
  • CYP3A5 Competitive Inhibitor

 Advantages and Limitations
  • Model developed to predict the impact of CYP3A4.
  • fm,CYP3A4 was optimized with clinical DDI data with ketoconazole.
  • Model recovers PK data after IV administration and single and multiple oral doses to healthy volunteers.
  • Model was used to evaluate the impact of hepatic impairment.
  • Perpetrator DDI not verified with clinical data.

 Model Compound Files
  • v18_darunavir_wagner. cmpz
  • v18_darunavir_600_mg_wagner. wksz

Publication – MODEL 2

Colbers, A., Greupink, R., Litjens, C., Burger, D., & Russel, F. G. (2016). Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy. Clinical pharmacokinetics, 55(3), 381–396. 

 Simcyp Version

V13

 Published Model Application

Prediction of exposure in pregnancy

 Absorption Model
  • ADAM (transporter efflux and influx included)
 Volume of Distribution Details
  • Full (permeability liver model, transporter efflux and influx included)

 Route of Elimination
  • CYP3A4 and renal clearance
  • ‘Bottom-up’ approach for CYP3A4 clearance from HLM data
  • Non-linear CYP3A4 kinetics

 Perpetrator DDI
  • None

 Advantages and Limitations
  • Model developed to extrapolate darunavir pharmacokinetics in pregnancy.
  • CYP3A4 enzyme kinetics derived from HLM data only.
  • Linked with ritonavir PBPK model.
  • Model recovers single dose PK data with and without ritonavir

 Model Compound Files
  • v18_darunavir_colbers. cmpz
  • v18_darunavir_600_mg_colbers. wksz
  • v18_darunavir_with_ritonavir_colbers. wksz
Search Score: 1
Dolutegravir
Model Files Publication

Brand Name: Tivicay

Disease: HIV

Drug Class: HIV integrase inhibitor

Version: 21

Date Updated: March 2023

The model at-a-glance

 Absorption Model

ADAM (precipitation with solution)
 Volume of Distribution Details

Full PBPK (Method 3)

 Route of Elimination
  • CYP3A4 = 21%; UGT1A1 = 51%; Additional HLM = 28%

 Perpetrator DDI
  • OCT2
  • MATE

 Validation

Model can recover positive food effect for single and multiple dose.

The UGT1A1 fm was verified against UGT1A1 genotype study and with rifampin and atazanavir DDI studies. The fm of CYP3A4 was verified against nevirapine, rifabutin, rifampin, atazanavir, efavirenz, and carbamazepine.

One clinical study in which dolutegravir was administered with metformin was used to verify the Ki of OCT2 and MATE.

Nine clinical DDI studies where dolutegravir was administered with either nevirapine, rifampicin, rifabutin, ritonavir, atazanavir, efavirenz, and carbamazepine were used to verify the PBPK model. In comparison of predicted vs. observed AUC, 100% of the studies were 2-fold and 67% were within 1.25-fold.

 Limitations

DDI with efavirenz and carbamazepine are underpredicted, likely because efavirenz and carbamazepine are inducers of UGT1A1 which is not considered in the current efavirenz and carbamazepine compound files.
Search Score: 1
Hydroxychloroquine_V18R1_PekingUniversityThirdHospital_20200323
Model Files Publication
The HCQ file was developed by Peking University Third Hospital and kindly shared on our Members Area. Please cite the original reference in which the file was presented (see link to publication) and please share your simulation results ASAP. Considering the current public health situation, we are happy to coordinate the simulation efforts around this PBPK model. The submitted compound file for HCQ is using first order absorption model, full-PBPK, Method 2. Perfusion limited lung model was developed. Additional organ was defined as lung and changed the tissue blood rate flow as 0.2. Clearance of HLM was estimated based on fm. It has been verified with a Caucasian healthy volunteer population library that was unmodified from the Sim-Healthy Volunteer library file. Please note a custom dosing for 5 days has been included in the file. https://pubmed.ncbi.nlm.nih.gov/32150618/
Search Score: 1
FostamatinibMetR406_V19R1_Pfizer_20210804
Model Files Publication
An optimized Rosuvastatin (V19) model was used and DDIs predominantly driven by gut BCRP inhibition are reasonably recovered. Altogether, the following inhibitors were used: Capmatinib Fenebrutinib Fostamatinib Itraconazole Zepatier The workspace represents the DDI between Rosuvastatin and Fostamatinib metabolite R406. Link to the publication with further details: http://doi.org/10.1002/psp4.12672
Search Score: 1

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