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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 82 Matches

Nicotine_MechKiM_V16R1_UniversityOfManchester_20210421
https://doi.org/10.1124/jpet.118.251413 Nicotine compound file with MechKiM

Brand Name(s) include: Viracept

Disease: HIV

Drug Class: Protease Inhibitor

Version: 21

Date Updated: March 2023

The model at-a-glance

 Absorption Model

ADAM (Solution)

 Volume of Distribution Details

Full PBPK (Method 2)

 Route of Elimination

  • CYP3A4 = 19.5 %, CYP2C19 = 33%, additional HLM = 20%, biliary clearance =26 %, renal clearance = 1.5% at steady state

 Perpetrator DDI

  • CYP3A4 competitive inhibition, Mechanism-Based Inhibition and Induction
  • P-gp Inhibition

 Validation

The refined model was able to recover clinically observed concentration-time profiles of nelfinavir following single and multiple dosing.

Six clinical DDI studies where nelfinavir was administered with either ritonavir, rifampicin, rifabutin, efavirenz, and nevirapine were used to verify the PBPK model of nevirapine as a victim. In comparison of predicted vs. observed AUC, 100% of the studies were within 1.5-fold.

Nine clinical DDI studies where nevirapine was administered with either alfentanil, midazolam, simvastatin, atorvastatin, rifabutin, or digoxin were used to verify the PBPK model of nevirapine as a perpetrator. In comparison of predicted vs. observed AUC, 100% of the studies were within 2-fold and 78% were within 1.25-fold.

 Limitations

  • Single oral dose exposure is underpredicted (generally within 2-fold)

Brand Name: Viramune

Disease: HIV

Drug Class: non-nucleoside reverse transcriptase inhibitor

Version: 21

Date Updated: March 2024

The model at-a-glance

 Absorption Model

First order

 Volume of Distribution Details

Full PBPK (Method 2)

 Route of Elimination

  • CYP2B6 = 35%; CYP2D6 = 12%; CYP3A4 = 45%; Additional HLM = 5%; Renal Clearance 3% at steady state

 Perpetrator DDI

  • CYP2B6 Induction
  • CYP3A4 Induction

 Validation

The refined model was able to recover clinically observed concentration-time profiles of nevirapine following single and multiple dosing.

Four clinical DDI studies where nevirapine was administered with either fluconazole, rifampin, or itraconazole were used to verify the PBPK model of nevirapine as a victim. In comparison of predicted vs. observed AUC, 100% of the studies were within 1.25-fold.

Two clinical DDI studies where nevirapine was administered with either itraconazole or quinidine were used to verify the PBPK model of nevirapine as a perpetrator. In comparison of predicted vs. observed AUC, 100% of the studies were within 1.5-fold.

 Limitations

  • There are no DDI studies where nevirapine was given as a single dose and so it is not possible to verify fm of CYP2B6 and CYP3A4 for a single dose.
  • There is no independent DDI study to verify induction of CYP2B6.
Non_Alcoholic_Steatohepatitis_Population_RES_V22R1_Simcyp_20231114

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