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.

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 110 Matches

Morphine&Morphine-3-Glucuronide_V18R1_UniversityOfNorthCarolina_20201005
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)
Montelukast_V14R1_AstraZeneca_20200427
Montelukast adult compound file for paediatric prediction.

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

 

Remdesivir&Metabolites_V18R1_Gilead_20210204
Remdesivir (GS-5734) and metabolites adult compound files Adult and pediatric (<40kg and >40kg) workspace files

|<

<

1

2

3

4

5

6

7

8

9

10

11

12

13

14

>

>|