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.

To contribute published user compound and/or population files, upload your files here: Upload Model Files

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

|<

<

1

2

3

4

5

6

7

8

9

10

11

12

13

14

>

>|

Found 101 Matches

Lumefantrine

Brand Name(s) include: Coartem (artemether, lumefantrine), Riamet (artemether, lumefantrine)

Disease: Malaria

Drug Class: Antimalarials

Related Files: Artemether – drug partner in fixed dose combinations

Date Updated: December 2022

The model at-a-glance

 Absorption Model

  • First-Order

 Volume of Distribution Details

  • Full PBPK (Method 2)

Note: Kp scalar and Kp adipose used

 Route of Elimination

CYP3A4 (40%); non-specific hepatic metabolism (60%)

 Perpetrator DDI

  • CYP2D6 Inhibitor

 Validation

  • Two clinical studies describing single dose exposure and two describing multiple dose exposure of lumefantrine were used to verify the PBPK model.
    • The single dose exposures were within 2-fold of observed for both studies.
    • The multiple dose exposures were within 1.25-fold of observed for both studies.
  • Clinical DDI studies with rifampicin and efavirenz in healthy volunteers where lumefantrine was the victim of CYP3A4-mediated DDIs were over-predicted (>2-fold) using the PBPK model.
  • An alternative clinical efavirenz DDI study in HIV patients and a clinical DDI with ritonavir in healthy volunteers were well predicted (within 1.25-fold of observed). As the effect of CYP3A4 inhibition was independently verified and there appeared to be variability in the extent of induction on lumefantrine PK, the fmCYP3A4 of 40% was considered verified.

 Limitations

  • Plasma concentrations of lumefantrine following a single dose are less accurately predicted than those following multiple dose administration. As the Day 7 plasma concentrations following repeat administration of lumefantrine, are more critical (linked to cure rates) than after the first dose, this was deemed acceptable.
  • The model can be used to prospectively predict CYP2D6-mediated DDIs but in the absence of verification of CYP2D6 inhibition, this should be accompanied by appropriate sensitivity analysis.​

 Updates in V19

  • Updates in vitro data based on new information
    • B:P ratio 0.6 -> 0.55
    • CYP2D6 Ki (µM) 2.2 -> 1.8

 

Praziquantel

Brand Name(s) include: Biltricide, Cysticide, Praquantel

Indication: Schistosomiasis and clonorchiasis/opisthorchiasis due to the liver flukes

Drug Class: Anthelmintic

Version: 22

Date Updated: February 2024

The model at-a-glance

 Absorption Model

  • ADAM, solid IR dosage form, permeability predicted by Caco-2 data, basolateral permeability scalar incorporated
 Volume of Distribution Details

Full model (method 3)

 Route of Elimination

  • fmCYP3A4 = 43.6, fmCYP1A2 = 41.4, fmCYP2C19 = 15.0

 Perpetrator DDI

  • Not included

 Validation

  • Model performance was verified in healthy adult volunteers and pediatric schistosomiasis patients. Eight clinical studies in adults (20 to 50 mg/kg PO) and one clinical study in children (20 to 60 mg/kg PO) were used for model verification. Across the adult healthy volunteer studies, eighteen of twenty-five simulated Cmax values and twenty-one of twenty-five simulated AUC values were within 2-fold of the observed data. For the pediatric study in schistosomiasis patients, eleven of twelve simulated Cmax and AUC values were within 2-fold of the observed data.
  • The fmCYP3A4 was verified through simulations of prazaquantel in the presence versus the absence of ketoconazole and rifampicin.

 Limitations

  • Model was developed using 20 mg/kg and 40 mg/kg PO adult data. Use of 20 to 50 mg/kg PO (healthy adult volunteers) and 20 to 60 mg/kg PO (pediatric schistosomiasis patients) were verified. Utility of the model outside these dose ranges is not confirmed.
  • Model assumes all CYP3A-dependent clearance is mediated by CYP3A4 (i.e., CYP3A5 is not included in the model)
  • Model is not verified for use as victim of CYP1A2 and CYP2C19 interactions
Aripiprazole_V12R2_USFDA_20160510

Note: additional dissolution data 0.5 hr 55% not captured in the supplemental materials of the publication

Fenebrutinib_V19R1_Pfizer_20210804

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 Fenebrutinib. Notes: - The fuGut in the inhibitor file is set as user input to 1. - An additional systemic clearance of 1.1 L/h is included in the submitted file. Link to the publication with further details: http://doi.org/10.1002/psp4.12672

|<

<

1

2

3

4

5

6

7

8

9

10

11

12

13

14

>

>|