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 137 Matches

Enfuviridine

Brand Name(s) include: Fuzeon

Disease: HIV

Drug Class: HIV Entry and Fusion Inhibitor

Date of Review: 2020

Number of Models Reviewed: 1

Number of Models added to the Repository: 1

The model at-a-glance

 Publication

Pan, X., Stader, F., Abduljalil, K., Gill, K. L., Johnson, T. N., Gardner, I., & Jamei, M. (2020). Development and Application of a Physiologically-Based Pharmacokinetic Model to Predict the Pharmacokinetics of Therapeutic Proteins from Full-term Neonates to Adolescents. The AAPS journal, 22(4), 76.

 Simcyp Version

V18

 Published Model Application

Prediction of exposure in noenates

 Absorption Model

First Order

 Volume of Distribution Details

Full PBPK

 Route of Elimination

  • Renal filtration
  • Additional systemic clearance

 Perpetrator DDI

  • None 

 Advantages and Limitations

  • Model was developed to predict the PK of enfuviridine in neonates and adolescents.
  • Model was verified in adult and pediatric populations.
  • Model was verified for IV and subcutaneous dosing.
  • Model was developed in V18.  Due to changes in the Simulator, the model would need to be revalidated for use in V20 and subsequent versions.

 Model Compound Files

  • v18_res_enfuviridine_simcyp_pan
  • v18_res_enfuviridine_simcyp_pan_sc_paed

Brand Name: Invirase (hard gel); Fortovase (soft gel)

Disease: HIV

Drug Class: protease inhibitor

Version: 21

Date Updated: March 2024

The model at-a-glance

 Absorption Model

First order (different absorption parameters for each formulation)

 Volume of Distribution Details

Minimal PBPK with Vsac and Q (Method 2)

 Route of Elimination

  • CYP3A4 = 95%; Additional HLM = 5%

 Perpetrator DDI

  • CYP3A4 Mechanism Based Inhibition

 Validation

The exposure of 1000mg BID saquinavir with 100 mg BID ritonavir regimen for hard gel were reasonably well recovered (3/3 within 2-fold). With the exception of the 1000 mg BID saquinavir with 100 mg BID ritonavir regimen for soft gel, the exposures of ritonavir-boosted regimens were well recovered (4/5 within 1.5-fold).

Ten clinical DDI studies where saquinavir (soft gel) was administered with either ritonavir, cimetidine, ketoconazole, rifampin, erythromycin, or rifabutin were used to verify the PBPK model of saquinavir as a victim. In comparison of predicted vs. observed AUC, 80% of the studies were within 2-fold.

Two clinical DDI studies where saquinavir (hard gel) was administered with either ritonavir or nelfinavir were used to verify the PBPK model of saquinavir (hard gel) as a victim. In comparison of predicted vs. observed AUC, 50% of the studies were within 2-fold.

Three clinical DDI studies where saquinavir was administered with either midazolam or rifabutin were used to verify the PBPK model of rifabutin (soft gel) as a perpetrator. In comparison of predicted vs. observed AUC, 100% of the studies were within 2-fold.

 Limitations

  • The variability within studies has presented a significant challenge to developing a single model to recover all data.
5HMT_V12R2_USFDA_20160510
Metabolite of fesoterodine. Note/correction: 1. PKa 9.3 instead of 7.6 (in supplemental materials) 2. the intrinsic clearance (CLint) values of CYP3A4 and CYP2D6 should be 0.085 and 1.455 uL/min/pmol enzyme 3. note simulation with ketoconazole, ketoconazole cmp file modified with p-gp inhibition constant (Ki) of 0.015 uM (assumed)
EsomeprazoleCapsule_V14R1_AstraZeneca_20200427
https://ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.905 Esomeprazole adult compound file for pediatric prediction. The following parameters need to be updated, as compared to Table 2 in the manuscript: Ka=1.331/h, tlag=1h, fu,gut=0.048

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