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 57 Matches

Brand Name(s) include: N/A

Disease: Malaria

Drug Class: Antimalarials

Date Updated: June 2021

Related Files: Amodiaquine (parent drug)

The model at-a-glance

  Absorption Model

  • N/A

  Volume of Distribution

  • Minimal PBPK (Method 2)

  Route of Elimination

  • CLPO (non-specific) and renal clearance

  Perpetrator DDI

  • CYP2D6

  Validation

  • Simulations based on 1 clinical study describing multiple dose exposure of DHEA and 1 DDI study where formation of DHEA was the victim of a CYP2C9 mediated DDI were both within 1.5-fold of the observed values.

  Limitations

  • Clinical data has not been used to verify DEAQ as a perpetrator of CYP2D6-mediated DDIs

  Updates in V19

  • Updated DEAQ Ki for CYP2D6

 

EsomeprazoleCapsule_V14R1_AstraZeneca_20200427
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.905 Esomeprazole adult compound file for pediatric prediction. The following parameters need to be updated, as compared to Table 2 in the manuscript: Ka=1.331/h, tlag=1h, fu,gut=0.048

Brand Name(s) include: Lariam, Mephaquin, Mefliam

Disease: Malaria

Drug Class: Antimalarials

Date Updated: November 2021

The model at-a-glance

  Absorption Model

First-Order

  Volume of Distribution

Full PBPK (Method 2)

  Route of Elimination

CYP3A4 (fm =100); renal clearance (fe = 0.05)

  Perpetrator DDI

  • CYP2C9 Inhibitor
  • CYP2D6 Inhibitor
  • CYP3A4 Inhibitor

  Validation

  • Six clinical studies describing single and multiple dose exposure of mefloquine were used the verify the PBPK model.  Most of the studies (83%) were within 1.5-fold, with all simulations falling within 2-fold of the observed values. 
  • Two clinical DDI studies where mefloquine was the victim of a CYP3A4-mediated DDI were accurately recovered using the PBPK model.

  Limitations

  • Only profiles of plasma concentrations assessed, many studies report blood concentrations​
  • Mefloquine has significant uptake into erythrocytes and haematocrit levels typically not reported​
  • Could be important in disease population (Possible time-varying B/P for Malaria patients?)​
  • Cmax for doses > 750 mg over predicted ​
  • fa possibly decreases with dose, more data needed to fully determine the cause​
  • Most literature data extracted from graphs of mean data, difficulty determining accurate early time points due to poor image quality​
  • Verification needed for perpetrator DDI assessment as literature data is unavailable at this time

  Updates in V19

  • Updated in vitro­ data
    • fup: 0.016 -> 0.015
    • B:P ratio 1.7 -> 1.1 and subsequent re-calculation of CLint using the retrograde approach
  • Converted model to full PBPK distribution model with Vss predicted through Method 2
  • Sensitivity analysis of ka

 

Tafenoquine

Brand Name(s) include: Arakoda, Krintafel

Disease: Malaria

Drug Class: Antimalarials

Date Updated: March 2022

The model at-a-glance

  Absorption Model

  • First-Order

  Volume of Distribution

  • Full PBPK (Method 3)
  • Note: Kp scalar used

  Route of Elimination

  • Undefined liver intrinsic clearance

  Perpetrator DDI

  • CYP2C9 Inhibitor
  • CYP3A4 Inhibitor

  Validation

  • Four clinical studies describing single and multiple dose exposure of tafenoquine were used to verify the PBPK model, although some of these provided PK profiles and no PK parameters and vice versa.  Of the clinical studies describing PK parameters, the model recovered 100% of the observed PK parameters within 1.5-fold (66% within 0.8-1.25-fold) and hence the model is considered predictive.  

  Limitations

  • Tafenoquine is administered with food to increase its exposure and minimize gastrointestinal side effects. The PBPK model was therefore developed to recover the PK of tafenoquine in the fed state.
  • It should be noted that in the absence of information defining the fm of drug metabolizing enzymes, an undefined liver intrinsic clearance is used in the model and hence the model is not able to simulate the liability of tafenoquine as a victim of DDIs.

 

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