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 13 Matches

Zepatier_V19R1_Pfizer_20210804
Model Files Publication
An optimized Rosuvastatin (V19) model was used and DDIs predominantly driven by gut BCRP inhibition are reasonably recovered. Altogether, the following inhibitors were used: Capmatinib Fenebrutinib Fostamatinib Itraconazole Zepatier The workspace represents the DDI between Rosuvastatin and Zepatier. Zepatier is an antiviral medicine that contains the active substances elbasvir and grazoprevir. The two compounds were simulated as Inhibitor 1 and Inhibitor 2, respectively. Link to the publication with further details: http://doi.org/10.1002/psp4.12672
Search Score: 11
Azithromycin
Model Files Publication

Brand Name(s) include: Zithromax

Disease: Malaria

Drug Class: Marcolide Antibiotic

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 > 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

 

Search Score: 1
Tenofovir
Model Files Publication

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
Search Score: 1
Olaparib_V16R1_AstraZeneca_20190717
Model Files Publication
Compound file from publication: Physiologically Based Pharmacokinetic Modeling for Olaparib Dosing Recommendations: Bridging Formulations, Drug Interactions, and Patient Populations Pilla Reddy, V., Bui, K., Scarfe, G., Zhou, D., Learoyd, M. (2018). Clinical Pharmacology and Therapeutics. https://doi.org/10.1002/cpt.1103 https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.1103 Note: The file is for the tablet form (Table 5 of the paper). The UGT1A1 Ki value of 48.4 µM is currently not included in the file.
Search Score: 1

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