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Article
Open AccessQuality Assurance of PBPK Modeling Platforms and Guidance on Building, Evaluating, Verifying and Applying PBPK Models Prudently under the Umbrella of Qualification: Why, When, What, How and By Whom?
Modeling and simulation emerges as a fundamental asset of drug development. Mechanistic modeling builds upon its strength to integrate various data to represent a detailed structural knowledge of a physiologic...
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Article
A Physiologically Based Pharmacokinetic Model of Voriconazole Integrating Time-Dependent Inhibition of CYP3A4, Genetic Polymorphisms of CYP2C19 and Predictions of Drug–Drug Interactions
Voriconazole, a first-line antifungal drug, exhibits nonlinear pharmacokinetics (PK), together with large interindividual variability but a narrow therapeutic range, and markedly inhibits cytochrome P450 (CYP)...
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Article
Open AccessPhysiologically Based Pharmacokinetic Models for Prediction of Complex CYP2C8 and OATP1B1 (SLCO1B1) Drug–Drug–Gene Interactions: A Modeling Network of Gemfibrozil, Repaglinide, Pioglitazone, Rifampicin, Clarithromycin and Itraconazole
Drug–drug interactions (DDIs) and drug–gene interactions (DGIs) pose a serious health risk that can be avoided by dose adaptation. These interactions are investigated in strictly controlled setups, quantifying...
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Article
Clarithromycin, Midazolam, and Digoxin: Application of PBPK Modeling to Gain New Insights into Drug–Drug Interactions and Co-medication Regimens
Clarithromycin is a substrate and mechanism-based inhibitor of cytochrome P450 (CYP) 3A4 as well as a substrate and competitive inhibitor of P-glycoprotein (P-gp) and organic anion-transporting polypeptides (O...
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Article
A Modeling and Simulation Framework for Adverse Events in Erlotinib-Treated Non-Small-Cell Lung Cancer Patients
Treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treating non-small-cell lung cancer (NSCLC) and other cancers, is frequently associated with adverse events (AE)...
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Article
Author’s Reply to Kotlinska-Lemieszek: “Should Midazolam Drug–Drug Interactions Be of Concern to Palliative Care Physicians?”
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Article
A Semiphysiological Population Pharmacokinetic Model for Dynamic Inhibition of Liver and Gut Wall Cytochrome P450 3A by Voriconazole
Accurate predictions of cytochrome P450 (CYP) 3A-mediated drug-drug interactions (DDIs) account for dynamic changes of CYP3A activity at both major expression sites (liver and gut wall) by considering the full...