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 69 Matches

Darolutamide_RES_V21R1_Simcyp_20230615
Model Files Publication

The RES-Darolutamide_V21 model has been developed primarily as inhibitor of hepatic OATP1B1 and OATP1B3, and intestinal BCRP using the New GI physiology in Simcyp V21 with altered GI tract population inputs that became default in V22. Darolutamide shows dose proportional PK between 100 to 700 mg BID. It is a BSCII compound, where the metabolite is a potent BCRP-inhibitor too. Darolutamide is possibly a weak CYP3A inducer in the clinic. The back-conversion of Keto-darolutamide to Darolutamide is efficiently catalyzed via cytosolic AKR1C3 (in vitro). This back-conversion is also observed in incubations of feces under anaerobic conditions (in vitro). In the compound fit-for-purpose compound file, the back-conversion was fixed to recover the concentration time profile for the 600 mg BID as this was the dose for the reported Rosuvastatin DDI. Note that two workspaces need to be run to simulate the Darolutamide DDI and then the results have to be combined. This is due to having to switch the position of Darolutamide and rosuvastatin (limitations on functionality on inhibitory metabolite in the Simcyp Simulator currently).

Search Score: 1
Etravirine
Model Files Publication

Brand Name(s) include: Intelence

Disease: HIV

Drug Class: Non-nucleoside reverse transcriptase inhibitors

Date of Review: 2020

Number of Models Reviewed: 3

Number of Models added to the Repository: 1

The model at-a-glance

Matlab/Simbiology

 Publication

Moltó, J., Rajoli, R., Back, D., Valle, M., Miranda, C., Owen, A., Clotet, B., & Siccardi, M. (2017). Use of a physiologically based pharmacokinetic model to simulate drug-drug interactions between antineoplastic and antiretroviral drugs. The Journal of antimicrobial chemotherapy, 72(3), 805–811.

 Simcyp Version

Not a Simcyp model (Matlab/Simbiology)

 Published Model Application

Simulation of DDIs

 Absorption Model

Compartmental absorption 
 Volume of Distribution Details

Full PBPK

 Route of Elimination
  • CYP3A4 and CYP2C19

 Perpetrator DDI
  • CYP3A4 Induction

 Advantages and Limitations
  • Model developed in healthy volunteers to simulate DDIs between antineoplastic and antiretrovirals.
  • Only verified with one study.

 Model Compound Files
  • None

Matlab/Simbiology

 Publication

Rajoli, R. K., Back, D. J., Rannard, S., Freel Meyers, C. L., Flexner, C., Owen, A., & Siccardi, M. (2015). Physiologically Based Pharmacokinetic Modelling to Inform Development of Intramuscular Long-Acting Nanoformulations for HIV. Clinical pharmacokinetics, 54(6), 639–650.

 Simcyp Version

Not a Simcyp model (Matlab/Simbiology)

 Published Model Application

Long-acting injectable formulation assessment

 Absorption Model

Compartmental and transit model
 Volume of Distribution Details

Full PBPK

 Route of Elimination
  • CYP3A4 and CYP2C19

 Perpetrator DDI
  • CYP3A4 Induction

 Advantages and Limitations
  • Model developed in HIV patients in the fed state
  • Formulation dependent PK

 Model Compound Files
  • None

Version 17

 Publication

Litou, C., Turner, D. B., Holmstock, N., Ceulemans, J., Box, K. J., Kostewicz, E., Kuentz, M., Holm, R., & Dressman, J. (2020). Combining biorelevant in vitro and in silico tools to investigate the in vivo performance of the amorphous solid dispersion formulation of etravirine in the fed state. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 149, 105297.

 Simcyp Version

V17

 Published Model Application

Prediction of Food Effect

 Absorption Model

ADAM
 Volume of Distribution Details

Full PBPK

 Route of Elimination
  • CYP3A4 and CYP2C19
    •  Includes Michaelis–Menten kinetics

 Perpetrator DDI
  • None included

 Advantages and Limitations
  • Model developed to predict PK of drugs with amorphous solid dispersion.
  • Model was verified for single administration in fed state.
  • Model can capture single and multiple dose.
  • Model victim DDI has not been verified

 Model Compound Files
  • v17_res_etravirine_simcyp_litou
Search Score: 1
Piperaquine
Model Files Publication

Brand Name(s) include: Eurartesim

Disease: Malaria

Drug Class: Antimalarials

Date Updated: January 2022

Related Files: DHA (partner in fixed dose combination)

The model at-a-glance

  Absorption Model
  • First-Order (dose and food-dependent fa – saved in different models)

  Volume of Distribution

  • Full PBPK (Method 2)
  • Notes: Includes a Kp scalar and Kpadipose

  Route of Elimination
  • CYP3A4 (80%), CYP2C9 (10%), CYP2C19 (10%)

  Perpetrator DDI
  • CYP3A4 Inhibitor

  Validation

  • Two clinical studies with fasted and fed groups at varying dose levels describing single and multiple dose exposure of piperaquine were used to verify the PBPK model. All of the simulated studies were within 1.5-fold of the observed values. 
  • A clinical DDI study where piperaquine was the victim of a CYP3A4-mediated DDI was accurately recovered using the PBPK model as well as a CYP3A4 perpetrator DDI with the sensitive substrate midazolam.

  Limitations
  • Requires separate files for low and high dose due to dose-dependant fa​
  • Cmax overprediction, likely due to formulation differences​
  • Additional verification for DDIs would be ideal although studies are currently not available in literature

  Updates in V19
  • Updated in vitro­ data
  • LogP
  • Converted model to full PBPK with Vss predicted through Method 2

 

Search Score: 1
Sulfadoxine
Model Files Publication

Brand Name(s) include: Fansidar

Disease: Malaria

Drug Class: Sulfonamide

Date Updated: March 2021

The model at-a-glance

  Absorption Model
  • First-Order

  Volume of Distribution

  • Minimal PBPK (User input Vss)

  Route of Elimination
  • Renal clearance (90%); non-specific hepatic metabolism (10%)

  Perpetrator DDI
  • None

  Validation

  • Four clinical studies describing single and multiple dose exposure of sulfadoxine were used to verify the PBPK model. In comparison of predicted vs. observed AUC, 100% of the studies were within 2-fold and 75% were within 1.5-fold. 

  Limitations
  • In the absence of adequate data on the metabolism and excretion of sulfadoxine, it was assumed that 90% was cleared renally and 10% was metabolized by the liver.

  Updates in V19
  • Updated in vitro­ data
    • LogP: 4.22 -> 0.54

 

Search Score: 1

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