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Brand Name(s) include: Daraprim
Disease: Malaria
Drug Class: Antimalarials
Date Updated: November 2021
Absorption Model |
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Volume of Distribution |
Note: Kp scalar used |
Route of Elimination |
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Perpetrator DDI |
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Validation |
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Limitations |
The current model does not mechanistically describe the absorption of pyrimethamine as the ADAM model over-predicts the extent of absorption. Although pyrimethamine is described as well absorbed in some literature, further analysis of the IV and PO data did not support this. |
Updates in V19 |
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Prepared: June 2023 The RES-Eltrombopag_V21 model has been developed primarily as an 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. The file is verified as tablet in the fasted state as that formulation was used in the Rosuvastatin DDI (Allred et al., 2011). The PK for Eltrombopag was evaluated at 25mg, 50mg and 75mg SD; 50mg QD, 100mg QD, 150mg QD, and 200mg QD. Note, the Rosuvastatin DDI with 75mg QD was used to fit the BCRP component in Rosuvastatin V21 file using the New GI physiology. The BCRP component of Rosuvastatin was then verified with other BCRP-Inhibitors available on the members area (as specified in the attached document) or within the Simcyp Simulator. Allred, A. J., C. J. Bowen, J. W. Park, B. Peng, D. D. Williams, M. B. Wire, and E. Lee. 2011. “Eltrombopag Increases Plasma Rosuvastatin Exposure in Healthy Volunteers.” Journal Article. Br J Clin Pharmacol 72 (2): 321–29.
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