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 99 Matches

Lopinavir&Ritonavir_V13R2_USFDA_20190719
Compound files from publication: Physiologically Based Pharmacokinetic Modeling for Predicting the Effect of Intrinsic and Extrinsic Factors on Darunavir or Lopinavir Exposure Coadministered With Ritonavir Wagner, C., Zhao, P., Arya, V., Mullick, C., Struble, K. and Au, S (2017). https://doi.org/10.1002/jcph.936 /PMID#: 28569994 The compound file is the final model used for simulations in combination with ritonavir (submitted to repository referencing the same article). Correction: Ritonavir's pKa 2 should be 2.6, reported in Supp. Table 1 was 2.8 https://accp1.onlinelibrary.wiley.com/doi/full/10.1002/jcph.936
Selegiline&Metabolites_V18R2_Simcyp_Transdermal_20201007
PBPK model of Transdermal Selegiline along with its metabolites. Note 1: The workspace is set up to mimic the clinical data reported by Azzaro et al., Journal of Clinical Pharmacology, 2007;47:1256-1267 Pharmacokinetics and Absolute Bioavailability of Selegiline Following Treatment of Healthy Subjects With the Selegiline Transdermal System (6 mg/24 h): A Comparison With Oral Selegiline Capsules. Note 2: A 6 mg/24 h dose corresponds to the release rate from a 20 mg/20 cm2 patch. The EMSAM®, SELEGILINE TRANSDERMAL SYSTEM, drug label from November 2012 states "EMSAM systems are available in three sizes: 20 mg/20 cm2, 30 mg/30 cm2, and 40 mg/40 cm2 that deliver, on average, doses of 6 mg, 9 mg, or 12 mg, respectively, of selegiline over 24 hours."
Lumefantrine

Brand Name(s) include: Coartem (artemether, lumefantrine), Riamet (artemether, lumefantrine)

Disease: Malaria

Drug Class: Antimalarials

Related Files: Artemether – drug partner in fixed dose combinations

Date Updated: December 2022

The model at-a-glance

 Absorption Model

  • First-Order

 Volume of Distribution Details

  • Full PBPK (Method 2)

Note: Kp scalar and Kp adipose used

 Route of Elimination

CYP3A4 (40%); non-specific hepatic metabolism (60%)

 Perpetrator DDI

  • CYP2D6 Inhibitor

 Validation

  • Two clinical studies describing single dose exposure and two describing multiple dose exposure of lumefantrine were used to verify the PBPK model.
    • The single dose exposures were within 2-fold of observed for both studies.
    • The multiple dose exposures were within 1.25-fold of observed for both studies.
  • Clinical DDI studies with rifampicin and efavirenz in healthy volunteers where lumefantrine was the victim of CYP3A4-mediated DDIs were over-predicted (>2-fold) using the PBPK model.
  • An alternative clinical efavirenz DDI study in HIV patients and a clinical DDI with ritonavir in healthy volunteers were well predicted (within 1.25-fold of observed). As the effect of CYP3A4 inhibition was independently verified and there appeared to be variability in the extent of induction on lumefantrine PK, the fmCYP3A4 of 40% was considered verified.

 Limitations

  • Plasma concentrations of lumefantrine following a single dose are less accurately predicted than those following multiple dose administration. As the Day 7 plasma concentrations following repeat administration of lumefantrine, are more critical (linked to cure rates) than after the first dose, this was deemed acceptable.
  • The model can be used to prospectively predict CYP2D6-mediated DDIs but in the absence of verification of CYP2D6 inhibition, this should be accompanied by appropriate sensitivity analysis.​

 Updates in V19

  • Updates in vitro data based on new information
    • B:P ratio 0.6 -> 0.55
    • CYP2D6 Ki (µM) 2.2 -> 1.8

 

Fostamatinib_RES_V21R1_Simcyp_20230615

Prepared: June 2023 The RES-Fostamatinib-R406_V21 model has been developed primarily as inhibitor of intestinal BCRP using the New GI physiology in Simcyp V21 with altered GI tract population inputs that became default in V22. Fostamatinib rapidly cleaved (hydrolyzed) to R406 (active moiety) in the gut by alkaline phosphatases. Thus, the Fit-for-purpose file with an in vivo CL/F is modelling the metabolite and not the parent. The verification was performed for 100-150 mg SD and BID. The Rosuvastatin DDI uses 100 mg BID. Example workspaces for the metabolite PK and the DDI with Rosuvastatin are attached. The BCRP component of Rosuvastatin (V21 using the New GI physiology) was optimised using Eltrombopag and then verified with other BCRP-Inhibitors available on the members area or within the Simcyp Simulator, see attached ‘BCRP-Inhibitor V21’ document for details.

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