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 Absorption Model

• ADAM, solid IR dosage form, permeability predicted by Caco-2 data, basolateral permeability scalar incorporated

Full model (method 3)

 Route of Elimination

• fm_CYP3A4 = 43.6, fm_CYP1A2 = 41.4, fm_CYP2C19 = 15.0

 Perpetrator DDI

• Not included

 Validation

• Model performance was verified in healthy adult volunteers and pediatric schistosomiasis patients. Eight clinical studies in adults (20 to 50 mg/kg PO) and one clinical study in children (20 to 60 mg/kg PO) were used for model verification. Across the adult healthy volunteer studies, eighteen of twenty-five simulated C_max values and twenty-one of twenty-five simulated AUC values were within 2-fold of the observed data. For the pediatric study in schistosomiasis patients, eleven of twelve simulated C_max and AUC values were within 2-fold of the observed data.
• The fm_CYP3A4 was verified through simulations of prazaquantel in the presence versus the absence of ketoconazole and rifampicin.

 Limitations

• Model was developed using 20 mg/kg and 40 mg/kg PO adult data. Use of 20 to 50 mg/kg PO (healthy adult volunteers) and 20 to 60 mg/kg PO (pediatric schistosomiasis patients) were verified. Utility of the model outside these dose ranges is not confirmed.
• Model assumes all CYP3A-dependent clearance is mediated by CYP3A4 (i.e., CYP3A5 is not included in the model)
• Model is not verified for use as victim of CYP1A2 and CYP2C19 interactions