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.
You can use a suffix operator (*) as the placeholder for end of a term. The query must start with at least one alphanumeric character before the suffix operator. E.g., Rifam* will get you “Rifampicin” and “Rifampin”. For more advanced searching tips click here.
Brand Name(s) include: Prezista, Prezcobix, Rezolsta
Disease: HIV
Drug Class: Antiretroviral
Date of Review: 2020
Number of Models Reviewed: 2
Number of Models added to the Repository: 2
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Publication – MODEL 1 |
Wagner et al., Physiologically-Based Pharmacokinetic Modeling for Predicting the Effect of Intrinsic and Extrinsic Factors on Darunavir or Lopinavir Exposure Co-administered with Ritonavir. J Clin Pharmacol. 2017 October ; 57(10): 1295–1304. (FDA model) |
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Simcyp Version |
V13 |
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Published Model Application |
Prediction of exposure in hepatic impairment |
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Absorption Model |
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| Volume of Distribution Details |
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Route of Elimination |
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Perpetrator DDI |
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Advantages and Limitations |
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Model Compound Files |
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Publication – MODEL 2 |
Colbers, A., Greupink, R., Litjens, C., Burger, D., & Russel, F. G. (2016). Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy. Clinical pharmacokinetics, 55(3), 381–396. |
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Simcyp Version |
V13 |
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Published Model Application |
Prediction of exposure in pregnancy |
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Absorption Model |
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| Volume of Distribution Details |
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Route of Elimination |
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Perpetrator DDI |
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Advantages and Limitations |
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Model Compound Files |
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Brand Name: Tivicay
Disease: HIV
Drug Class: HIV integrase inhibitor
Version: 21
Date Updated: March 2023
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Absorption Model |
ADAM (precipitation with solution) |
| Volume of Distribution Details |
Full PBPK (Method 3) |
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Route of Elimination |
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Perpetrator DDI |
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Validation |
Model can recover positive food effect for single and multiple dose. The UGT1A1 fm was verified against UGT1A1 genotype study and with rifampin and atazanavir DDI studies. The fm of CYP3A4 was verified against nevirapine, rifabutin, rifampin, atazanavir, efavirenz, and carbamazepine. One clinical study in which dolutegravir was administered with metformin was used to verify the Ki of OCT2 and MATE. Nine clinical DDI studies where dolutegravir was administered with either nevirapine, rifampicin, rifabutin, ritonavir, atazanavir, efavirenz, and carbamazepine were used to verify the PBPK model. In comparison of predicted vs. observed AUC, 100% of the studies were 2-fold and 67% were within 1.25-fold. |
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Limitations |
DDI with efavirenz and carbamazepine are underpredicted, likely because efavirenz and carbamazepine are inducers of UGT1A1 which is not considered in the current efavirenz and carbamazepine compound files. |
The RES-Darolutamide_V21 model has been developed primarily as inhibitor of hepatic OATP1B1 and OATP1B3, and intestinal BCRP using the New GI physiology in Simcyp V21 with altered GI tract population inputs that became default in V22. Darolutamide shows dose proportional PK between 100 to 700 mg BID. It is a BSCII compound, where the metabolite is a potent BCRP-inhibitor too. Darolutamide is possibly a weak CYP3A inducer in the clinic. The back-conversion of Keto-darolutamide to Darolutamide is efficiently catalyzed via cytosolic AKR1C3 (in vitro). This back-conversion is also observed in incubations of feces under anaerobic conditions (in vitro). In the compound fit-for-purpose compound file, the back-conversion was fixed to recover the concentration time profile for the 600 mg BID as this was the dose for the reported Rosuvastatin DDI. Note that two workspaces need to be run to simulate the Darolutamide DDI and then the results have to be combined. This is due to having to switch the position of Darolutamide and rosuvastatin (limitations on functionality on inhibitory metabolite in the Simcyp Simulator currently).
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3 |