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 126 Matches

Artemether
Model Files Publication

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

 

Search Score: 1
Dasabuvir_RES_V21R1_Simcyp_20220309
Model Files Publication

The V21 RES-Dasabuvir model has been developed as a substrate of CYP2C8 and CYP3A4. Compound file and performance summary are available.

Search Score: 1
Docetaxel_RES_V17R1_Simcyp_20180228
Model Files Publication

Simcyp developed Docetaxel compound file. Compound summary document included. This was developed as a research file and its current status and limitations are outlined in summary document.

Search Score: 1
Dolutegravir_RES_V23R1_Simcyp_20240404
Model Files Publication

Simcyp developed dolutegravir compound file. Compound summary including an outline on the current status and limitations included.

The RES-Dolutegravir model has been developed primarily as a UGT1A1 and CYP3A4 substrate, and as an inhibitor of renal MATE1 and OCT2 transporters. MATE1 and OCT2 inhibition parameters have been optimized to capture impact of dolutegravir on metformin pharmacokinetics but have not been independently verified. In vitro observed inhibition of MATE2-K by dolutegravir has not been included as the parameter could not be optimized and verified with the substrate models and clinical data available at the time of dolutegravir model development.

Search Score: 1

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