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 68 Matches

Brand Name(s) include: Viread

Disease: HIV

Drug Class: Nucleoside Reverse Transcriptase Inhibitors (NRTI)

Date of Review: 2020

Number of Models Reviewed: 3

Number of Models added to the Repository: 3

The model at-a-glance

Publication 

De Sousa Mendes, M., Chetty, M. Are Standard Doses of Renally-Excreted Antiretrovirals in Older Patients Appropriate: A PBPK Study Comparing Exposures in the Elderly Population With Those in Renal Impairment. Drugs R D 19, 339–350 (2019).

 Simcyp Version

V17

 Absorption Model

  • First-Order
 Volume of Distribution Details
  • Full

 Route of Elimination

  • Renal Clearance
  • Additional non-specific clearance

 Perpetrator DDI

  • None

 Advantages and Limitations

  • Developed in healthy volunteers to extrapolate to elderly and renally impaired populations

 Model Compound Files

  • v17_res_tenofovir_simcyp_desousamendez_2019_SD.wksz
  • v17_res_tenofovir_simcyp_desousamendez_2019_young_pop.wksz
  • v17_res_tenofovir_simcyp_desousamendez_2019_elderly_pop.wksz

Publication 

Liu S N, Desta Z, Gufford B T. Probenecid‐Boosted Tenofovir: A Physiologically‐Based Pharmacokinetic Model‐Informed Strategy for On‐Demand HIV Preexposure Prophylaxis[J]. CPT: pharmacometrics& systems pharmacology, 2020, 9(1): 40- 47.

 Simcyp Version

V15

 Absorption Model

  • First-Order
 Volume of Distribution Details
  • Full

 Route of Elimination

  • Permeability-limited kidney model
  • Renal uptake into the kidney by OAT1 and OAT3
  • Renal efflux by MRP4
  • Hepatic elimination with sinusoidal uptake

 Perpetrator DDI

  • None

 Advantages and Limitations

  • Based on De Sousa Mendes (2015) paper, OAT3 kinetics added to model.
  • Model used to simulate tenofovir as a victim of probenecid DDI.

 Model Compound Files

  • v15_res_tenofovir_simcyp_Liu_2020.wksz
  • v15_res_tenofovir_simcyp_Liu_2020.cmpz

Publication 

De Sousa Mendes M, Hirt D, Urien S, Valade E, Bouazza N, Foissac F, Blanche S, Treluyer JM, Benaboud S. Physiologically-based pharmacokinetic modeling of renally excreted antiretroviral drugs in pregnant women. Br J Clin Pharmacol. 2015 Nov;80(5):1031-41.

 Simcyp Version

V13

 Published Model Application

Prediction of exposure in pregnancy

 Absorption Model

  • First-Order
 Volume of Distribution Details
  • Full

 Route of Elimination

  • Renal clearance with uptake by OAT1 and efflux by MRP4
  • Hepatic transporter clearance
  • Additional non-specific clearance

 Perpetrator DDI

  • None

 Advantages and Limitations

  • Model developed to simulate PK in pregnant women after development in healthy populations.
  • Low risk of DDI.
  • Tenofovir is administered as a rapidly hydrolyzed prodrug (Tenofovir disoproxil fumarate). The 300 mg TDF dose was implemented as a 136 mg of tenofovir. The PK of the prodrug is not considered.
  • Incorporates high degree of variability (%CV 60%) in the fraction absorbed.

 Model Compound Files

  • v13_res_tenofovir_simcyp_desousamendez_2015_1mg_kg.wksz
  • v13_res_tenofovir_simcyp_desousamendez_2015_3mg_kg.wksz
  • v13_res_tenofovir_simcyp_desousamendez_2015_PO.wksz
  • v13_res_tenofovir_simcyp_desousamendez_2015.cmpz
Praziquantel

Brand Name(s) include: Biltricide, Cysticide, Praquantel

Indication: Schistosomiasis and clonorchiasis/opisthorchiasis due to the liver flukes

Drug Class: Anthelmintic

Version: 22

Date Updated: February 2024

The model at-a-glance

 Absorption Model

  • ADAM, solid IR dosage form, permeability predicted by Caco-2 data, basolateral permeability scalar incorporated
 Volume of Distribution Details

Full model (method 3)

 Route of Elimination

  • fmCYP3A4 = 43.6, fmCYP1A2 = 41.4, fmCYP2C19 = 15.0

 Perpetrator DDI

  • Not included

 Validation

  • Model performance was verified in healthy adult volunteers and pediatric schistosomiasis patients. Eight clinical studies in adults (20 to 50 mg/kg PO) and one clinical study in children (20 to 60 mg/kg PO) were used for model verification. Across the adult healthy volunteer studies, eighteen of twenty-five simulated Cmax values and twenty-one of twenty-five simulated AUC values were within 2-fold of the observed data. For the pediatric study in schistosomiasis patients, eleven of twelve simulated Cmax and AUC values were within 2-fold of the observed data.
  • The fmCYP3A4 was verified through simulations of prazaquantel in the presence versus the absence of ketoconazole and rifampicin.

 Limitations

  • Model was developed using 20 mg/kg and 40 mg/kg PO adult data. Use of 20 to 50 mg/kg PO (healthy adult volunteers) and 20 to 60 mg/kg PO (pediatric schistosomiasis patients) were verified. Utility of the model outside these dose ranges is not confirmed.
  • Model assumes all CYP3A-dependent clearance is mediated by CYP3A4 (i.e., CYP3A5 is not included in the model)
  • Model is not verified for use as victim of CYP1A2 and CYP2C19 interactions
Amodiaquine

Brand Name(s) include: Basoquin, Camoquin, Flavoquin, Coarsucam

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)

  Route of Elimination

CYP2C8 = 72%; Additional HLM = 28%

  Perpetrator DDI

  • CYP2D6 

  Validation

  • Four clinical studies describing single and multiple dose exposure of amodiaquine were used to verify the PBPK model. In comparison of predicted vs. observed AUC, 75% of the studies were 2-fold and 50% were within 1.5-fold. A clinical DDI study where amodiaquine was the victim of a CYP2C8-mediated DDI was accurately recovered using the PBPK model.

  Limitations

  • Clinical data has not been used to verify amodiaquine as a perpetrator of CYP2D6-mediated DDIs

  Updates in V19

  • Updated in vitro­ data
    • fu: 0.033 -> 0.089
    • B:P: 1.3 -> 1.1
    • DEAQ Ki for CYP2D6 (µM) – 1.7 -> 1.6
  • Converted from minimal PBPK model to full PBPK model
    • Recalculated retrograde clearance for CYP2C8 CLint and additional HLM CLint

 

Brand Name(s) include: Epivir

Disease: HIV

Drug Class: Nucleoside reverse transcriptase inhibitor

Date of Review: 2020

Number of Models Reviewed: 3

Number of Models added to the Repository: 3

The model at-a-glance

Version 13

 Publication

De Sousa Mendes, M., Hirt, D., Urien, S., Valade, E., Bouazza, N., Foissac, F., Blanche, S., Treluyer, J. M., & Benaboud, S. (2015). Physiologically-based pharmacokinetic modeling of renally excreted antiretroviral drugs in pregnant women. British journal of clinical pharmacology, 80(5), 1031–1041.

 Simcyp Version

V13

 Published Model Application

Prediction of exposure in pregnancy

 Absorption Model

First Order

 Volume of Distribution Details

Full PBPK

 Route of Elimination

  • Renal Elimination
  • Includes uptake by OCT2 and efflux by MRP4 in the kidney

 Perpetrator DDI

  • None 

 Advantages and Limitations

  • Model developed in healthy volunteers and verified in pregnant women.

 Model Compound Files

  • v13_res_lamivudine_simcyp_mendex2015

Version 17

 

 Publication

De Sousa Mendes M, Chetty M. Are Standard Doses of Renally-Excreted Antiretrovirals in Older Patients Appropriate: A PBPK Study Comparing Exposures in the Elderly Population With Those in Renal Impairment. Drugs R D. 2019 Dec;19(4):339-350.

 Simcyp Version

V17

 Published Model Application

Prediction of exposure in renal impairment

 Absorption Model

First Order

 Volume of Distribution Details

Full PBPK

 Route of Elimination

  • Renal Elimination
  • Additional non-specific clearance

 Perpetrator DDI

  • None 

 Advantages and Limitations

  • Model developed to extrapolate elderly populations and renally impaired populations.
  • Model was verified in the elderly population

 Model Compound Files

  • v17_res_ lamivudine_simcyp_mendex2019

Version 18

 Publication

Shah, K., Fischetti, B., Cha, A., & Taft, D. R. (2020). Using PBPK Modeling to Predict Drug Exposure and Support Dosage Adjustments in Patients With Renal Impairment: An Example with Lamivudine. Current drug discovery technologies, 17(3), 387–396.

 Simcyp Version

V18

 Published Model Application

Prediction of exposure in renal impairment

 Absorption Model

First Order

 Volume of Distribution Details

Full (mechanistic kidney model)

 Route of Elimination

  • Renal Elimination
  • Includes uptake by OCT2 and efflux by MATE in the kidney

 Perpetrator DDI

  • None 

 Advantages and Limitations

  • Model developed to renally impaired populations.

 Model Compound Files

  • v18_res_ lamivudine_simcyp_shah2020

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