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 127 Matches

Morphine&Morphine-3-Glucuronide_V18R1_UniversityOfNorthCarolina_20201005
Model Files Publication
The submitted workspace file is for Morphine and Morphine-3-glucuronide compound files, with a full PBPK distribution model, ADAM and permeability-limited liver. The model also includes enterohepatic recycling and cleavage of the glucuronide in the gut lumen. The Sim-Healthy Volunteers population library was modified with regards to the relative enzyme abundance of luminal deglucuronidation. The setting in the workspace reflects the trial design from Stuart-Harris et al., 2000. Stuart-Harris R, Joel SP, McDonald P, Currow D, Slevin ML. The pharmacokinetics of morphine and morphine glucuronide metabolites after subcutaneous bolus injection and subcutaneous infusion of morphine. Br J Clin Pharmacol 49 207-214. (2000)
Search Score: 1
Tenofovir_V18R1_Simcyp_20200212
Model Files Publication
Tenofovir dispoproxil fumarate: the dose was calculated to correct for the prodrug. FO, full PBPK model with method 2 and KP scalar. Mainly renally excreted (renal clearance input, not mechanistic).
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
Quinine
Model Files Publication

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

 

Search Score: 1

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