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 89 Matches

Piperaquine

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

 

Sulfadoxine

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

 

Brand Name(s) include: Qualaquin

Disease: Malaria

Drug Class: Antimalarials

Date Updated: 2021

The model at-a-glance

  Absorption Model

First-Order

  Volume of Distribution

Minimal PBPK (Method 1)

  Route of Elimination

CYP3A4 (fm = 0.50); renal clearance (fe = 0.1)

  Perpetrator DDI

  • CYP2D6 Inhibitor

  Validation

  • Three clinical studies describing Quinine PK were identified for model verification.
  • Three clinical DDI studies where quinine was the victim of CYP-mediated DDIs were used to verify the PBPK model.  All studies were well recovered with simulated Cmax and AUC GMRs within 1.5-fold of the observed

  Limitations

  • The Simcyp quinine PBPK model was able to recover interactions CYP3A inducers and inhibitors with reasonable accuracy.
  • Verification needed for perpetrator DDI assessment as literature data is unavailable at this time.

  Updates in V19

  • Updated in vitro­ data
    • fup: 0.199 -> 0.37
    • Caco-2 A -> B Permeability: 70 x 10-6 cm/s -> 39 x 10-6 cm/s
    • Propranolol reference Permeability: 101 x 10-6 cm/s -> 45 x 10-6 cm/s
  • Minimal PBPK with Vss predicted through Method 1
    • Updated retrograde clearance

 

Bosutinib_V18R2_Pfizer_20240809

The Bosutinib model uses a full PBPK distribution model (Method 2) and ADAM, where intestinal P-gp is accounted for (Km=0.38 uM, Jmax = 15.45 pmol/min/cm­2, RAF = 4). The elimination is described via HLM clearance and assigned to CYP3A4, and a user defined renal clearance. An Immediate Release formulation is simulated with a user-defined solubility-pH profile. The performance of the file is described in Yamazaki et al., 2018 (Application of Physiologically Based Pharmacokinetic Modeling in Understanding Bosutinib Drug-Drug Interactions: Importance of Intestinal P-Glycoprotein - PubMed (nih.gov). In a follow-up paper using V18R2, the inputs for intestinal P-gp were updated (Km = 0.58 uM, Jmax = 67.4 pmol/min/cm­2, REF = 1) based on Caco-2 data analysed in SIVA (Pan et al., 2021, Unraveling pleiotropic effects of rifampicin by using physiologically based pharmacokinetic modeling: Assessing the induction magnitude of P-glycoprotein-cytochrome P450 3A4 dual substrates - PubMed (nih.gov)).

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