ArticleFrontiers in pharmacology2022
Prediction for optimal dosage of pazopanib under various clinical situations using physiologically based pharmacokinetic modeling.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 12 citations in OpenAlex.
- PBPK modeling predicts rilzabrutinib dose adjustments using BTK occupancy for CYP3A4 interactions and hepatic impairment.Scientific reports · 2026Article
- Midazolam Dosing During CRRT: A Combined Ex Vivo and Physiologically-Based Pharmacokinetic Approach.CPT: pharmacometrics & systems pharmacology · 2026Article
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Predicting drug-drug interactions and optimal dosing of betrixaban with physiologically based pharmacokinetic modeling in patients with renal impairment who were coadministered with P-glycoprotein inhibitors.The Journal of international medical research · 2025Article
- Simulation of Antral Conditions for Estimating Drug Apparent Equilibrium Solubility after a High-Calorie, High-Fat Meal.Molecular pharmaceutics · 2025Article
- Application of a Novel Dissolution Medium with Lipids for In Vitro Simulation of the Postprandial Gastric Content.Pharmaceutics · 2024Article
- Identification, screening, and comprehensive evaluation of novel thrombin inhibitory peptides from the hirudo produced using pepsin.Frontiers in pharmacology · 2024Article
- Physiologically-based pharmacokinetic modeling for optimal dosage prediction of olaparib when co-administered with CYP3A4 modulators and in patients with hepatic/renal impairment.Scientific reports · 2023Article
- Article
- Prediction of trough concentration and ALK occupancy in plasma and cerebrospinal fluid using physiologically based pharmacokinetic modeling of crizotinib, alectinib, and lorlatinib.Frontiers in pharmacology · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to apply a physiologically based pharmacokinetic (PBPK) model to predict optimal dosing regimens of pazopanib (PAZ) for safe and effective administration when co-administered with CYP3A4 inhibitors, acid-reducing agents, food, and administered in patients with hepatic impairment. Here, we have successfully developed the population PBPK model and the predicted PK variables by this model matched well with the clinically observed data. Most ratios of prediction to observation were between 0.5 and 2.0. Suitable dosage modifications of PAZ have been identified using the PBPK simulations in various situations, i.e., 200 mg once daily (OD) or 100 mg twice daily (BID) when co-administered with the two CYP3A4 inhibitors, 200 mg BID when simultaneously administered with food or 800 mg OD when avoiding food uptake simultaneously. Additionally, the PBPK model also suggested that dosing does not need to be adjusted when co-administered with esomeprazole and administration in patients with wild hepatic impairment. Furthermore, the PBPK model also suggested that PAZ is not recommended to be administered in patients with severe hepatic impairment. In summary, the present PBPK model can determine the optimal dosing adjustment recommendations in multiple clinical uses, which cannot be achieved by only focusing on AUC linear change of PK.
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