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

Found 99 Matches

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

 

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

 

Capmatinib_RES_V21R1_Simcyp_20230615

The RES-Capmatinib_V21 model has been developed primarily as an inhibitor of hepatic OATP1B1 and OATP1B3, and intestinal BCRP using the New GI physiology in Simcyp V21 with altered GI tract population inputs that became default for V22. The verification for 200mg SD, 400mg SD, 600mg SD is performed in the Sim-Healthy Volunteer population and for the 400 mg BID in the Sim-Cancer population. A multiple plasma protein approach is used, accounting for HSA, AGP, IgG and lipoprotein inputs for the populations. The metabolism is simulated using Cytosolic Oxidases (rhAO) and CYP3A4. The Rosuvastatin DDI is using a 400mg BID dosing for Capmatinib in the fasted state.

Eltrombopag_RES_V21R1_Simcyp_20230615

Prepared: June 2023 The RES-Eltrombopag_V21 model has been developed primarily as an inhibitor of hepatic OATP1B1 and OATP1B3, and intestinal BCRP using the New GI physiology in Simcyp V21 with altered GI tract population inputs that became default in V22. The file is verified as tablet in the fasted state as that formulation was used in the Rosuvastatin DDI (Allred et al., 2011). The PK for Eltrombopag was evaluated at 25mg, 50mg and 75mg SD; 50mg QD, 100mg QD, 150mg QD, and 200mg QD.  Note, the Rosuvastatin DDI with 75mg QD was used to fit the BCRP component in Rosuvastatin V21 file using the New GI physiology. The BCRP component of Rosuvastatin was then verified with other BCRP-Inhibitors available on the members area (as specified in the attached document) or within the Simcyp Simulator. Allred, A. J., C. J. Bowen, J. W. Park, B. Peng, D. D. Williams, M. B. Wire, and E. Lee. 2011. “Eltrombopag Increases Plasma Rosuvastatin Exposure in Healthy Volunteers.” Journal Article. Br J Clin Pharmacol 72 (2): 321–29.

|<

<

12

13

14

15

16

17

18

19

20

21

22

23

24

25

>

>|