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 123 Matches

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

 

Brand Name(s) include: Malarone

Disease: Malaria

Drug Class: Antimalarials

Date Updated: March 2021

The model at-a-glance

  Absorption Model

  • First-Order

  Volume of Distribution

  • Full PBPK (Method 2)

Note: A Kp scalar (0.04) was used in the model

  Route of Elimination

  • No metabolism; a biliary CLint was input based on clinical data

  Perpetrator DDI

  • None

  Validation

  • Two clinical studies describing single and multiple dose exposure of atovaquone were used to verify the PBPK model. 100% of studies were within 1.5-fold.

  Limitations

  • There are some data to suggest atovaquone is an inhibitor of BCRP.  This is currently not included within the model.

  Updates in V19

  • Updated in vitro­ data
    • LogP: 5.8 -> 8.4
    • Caco-2 Papp 164 > 300 x 10-6 cm/s
    • Propranolol Papp 101 x 10-6 cm/s
  • Optimized ka and tlag
  • Converted from minimal PBPK model to full PBPK model

 

Carboxyprimaquine

Disease: Malaria

Drug Class: Antimalarials

Date Updated: March 2022

Related Files:  Primaquine (parent)

The model at-a-glance

  Absorption Model

N/A

  Volume of Distribution

Full PBPK (Method 2)

  Route of Elimination

  • Formed from primaquine by MAO. This is entered as ‘user-UGT’ as a surrogate within the simulator
  • Pathway of elimination is not defined; elimination is assigned as IV clearance that was manually optimized to fit the clinical data

  Perpetrator DDI

  • None

  Validation

  • Six clinical studies describing single and multiple dose exposure of carboxyprimaquine were used to verify the PBPK model.  The AUC for all verification studies were within 1.5-fold of the observed values.

  Limitations

  • Clinical data for carboxyprimaquine is highly variable

  Updates in V19

  • Converted from minimal PBPK model to full PBPK model

 

Brand Name(s) include: Coartem

Disease: Malaria

Drug Class: Antimalarials

Date Updated: June 2021

The model at-a-glance

  Absorption Model

First-Order

  Volume of Distribution

  • Full PBPK (Method 2)

Note: A Kp scalar (0.5) was used in the model along with optimized partitioning into adipose tissue (Kp,adipose = 0.5) to recover the clinical observed data. 

  Route of Elimination

  • CYP2B6 and CYP3A4 (non-linear kinetics); incorporates autoinduction of CYP2B6

  Perpetrator DDI

  • Induction of CYP2B6

  Validation

  • Two clinical studies describing single dose exposure and two describing multiple dose exposure of artemether were used to verify the PBPK model.  The single dose exposures were within 1.5-fold of observed for both studies. The multiple dose exposures were slightly over-predicted at 2.02 and 2.63-fold for the two studies.  Clinical DDI studies with ketoconazole, rifampicin and efavirenz where artemether was the victim of CYP3A4 (and CYP2B6 for efavirenz)-mediated DDIs were accurately recovered (within 1.25-fold) using the PBPK model.  A clinical DDI study with efavirenz, where artemether was the perpetrator of a CYP2B6-mediated DDI was accurately recovered (within 1.25-fold) using the PBPK model. 

  Limitations

  • The tendency towards over-prediction of artemether exposure upon multiple dosing could indicate a greater extent of induction is required. However, any increase in induction potency resulted in under-prediction of single dose exposure, which is of greater importance for the therapeutic effect of artemether.

  Updates in V19

  • Updated in vitro­ data
    • fu: 0.083 -> 0.038
    • B:P: 1.7 -> 1.1
  • Optimized ka and tlag
  • Converted from minimal PBPK model to full PBPK model
    • Optimized CYP2B6 IndC50

 

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