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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 68 Matches

Levonorgestrel_RES_V21R1_Simcyp_20220401

The V21 RES-Levonorgestrel file has been developed as a substrate of CYP3A4. The file was developed to capture the pharmacokinetics after administration of Levonorgestrel alone or in combination with Ethinyl Estradiol. A workspace and performance summary are available. Levonorgestrel is known to bind to the plasma protein Sex Hormone Binding Globulin and this has been captured in the file by utilising the other protein option in the population.

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.

 

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.

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