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 57 Matches

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

 

Pitavastatin_RES_V20R1_Simcyp_20211102

The RES-Pitavastatin file was developed as a CYP2C9, UGT1A3/2B7, OATP1B1/1B3/2B1, NTCP substrate This document provides: 1. Examples of model performance 2. A summary of the key pharmacokinetic features of pitavastatin considered within the model.

Brand Name(s) include: Selzentry

Disease: HIV

Drug Class: HIV Entry and Fusion Inhibitor

Date of Review: 2020

Number of Models Reviewed: 3

Number of Models added to the Repository: 1

The model at-a-glance

 Publication

Kimoto, E., Vourvahis, M., Scialis, R. J., Eng, H., Rodrigues, A. D., & Varma, M. V. S. (2019). Mechanistic Evaluation of the Complex Drug-Drug Interactions of Maraviroc: Contribution of Cytochrome P450 3A, P-Glycoprotein and Organic Anion Transporting Polypeptide 1B1. Drug metabolism and disposition: the biological fate of chemicals, 47(5), 493–503.

 Simcyp Version

V15

 Published Model Application

DDI prediction

 Absorption Model

ADAM; includes P-gp in the intestines

 Volume of Distribution Details

Full PBPK

 Route of Elimination

  • CYP3A4
  • Renal clearance
  • Includes hepatic biliary clearance by OATP1B1

 Advantages and Limitations

  • Model was developed to evaluate DDI of maraviroc as victim.
  • Model was verified with IV and oral data.
  • Model was verified as a victim of interactions with ketoconazole, ritonavir, efavirenz and rifampin

 Model Compound Files

  • v15_res_maraviroc_simcyp_kimoto
  • v15_res_maraviroc_simcyp_kimoto_iv_3mg
  • v15_res_maraviroc_simcyp_kimoto_iv_10mg
  • v15_res_maraviroc_simcyp_kimoto_iv_30mg
  • v15_res_maraviroc_simcyp_kimoto_po_150mg_bid
Chlorpromazine

Brand Name(s) include: Thorazine, Largactil, Ormazine

Indication: Schizophrenia, manic-depression

Drug Class: Conventional anitpsychotic

Date Updated: March 2024

The model at-a-glance

  Absorption Model

  • First-Order, fa and ka predicted by Caco-2 data

  Volume of Distribution

  • Minimal (optimized to IV data)

  Route of Elimination

  • fmCYP3A4 = 80, fmCYP2D6 = 20

  Perpetrator DDI

  • Inhibition of CYP2D6

  Validation

  • Model performance was verified in healthy volunteers and psychiatric patients. Two clinical studies with IV administration (7 to 10 mg) and ten clinical studies with oral administration (25 to 200 mg) were used for model verification. Simulations for eight of eleven clinical studies with a reported AUC were within 2-fold of the observed value.
  • The fmCYP1A2 was verified through simulations of chlorpromazine in smokers and non-smokers. The fmCYP2D6­ was verified through simulations of chlorpromazine coadministered with and without quinidine.

  Limitations

  • Model was developed using 10 mg IV and 100 mg PO. Use of 7-10 mg IV dosing and oral doses of 100-200 mg were verified, but predictions of oral doses <100 mg PO are overestimated.
  • Model does not include P-gp efflux.
  • Model is not verified for use in perpetrator DDI simulations with CYP2D6 substrates.

 

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