Publications by authors named "D Teutonico"
Accurate prediction of a new compound's pharmacokinetic (PK) profile is pivotal for the success of drug discovery programs. An initial assessment of PK in preclinical species and humans is typically performed through allometric scaling and mathematical modeling. These methods use parameters estimated from in vitro or in vivo experiments, which although helpful for an initial estimation, require extensive animal experiments.
View Article and Find Full Text PDFSince the Open Source Initiative laid the foundation for the open source software environment in 1998, the popularity of free and open source software has been steadily increasing. Model-informed drug discovery and development (MID3), a key component of pharmaceutical research and development, heavily makes use of computational models which can be developed using various software including the Open Systems Pharmacology (OSP) software (PK-Sim/MoBi), a free and open source software tool for physiologically based pharmacokinetic (PBPK) modeling. In this study, we aimed to investigate the impact, application areas, and reach of the OSP software as well as the relationships and collaboration patterns between organizations having published OSP-related articles between 2017 and 2023.
View Article and Find Full Text PDFTusamitamab ravtansine is an antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody (IgG1) and DM4 payload. Even if DM4 and its main metabolite methyl-DM4 (Me-DM4) circulate at low concentrations after ADC administration, their potential as perpetrators of cytochrome P450 mediated drug-drug interaction was assessed. In vitro studies in human hepatocytes indicated that Me-DM4 elicited a clear concentration-dependent down regulation of cytochrome P450 enzymes (CYP3A4, 1A2, and 2B6).
View Article and Find Full Text PDFArticle Synopsis
- Quinidine is an antiarrhythmic drug that inhibits CYP2D6 and P-glycoprotein, making it important for studying drug-drug interactions (DDIs), but it's also affected by interactions with CYP3A4 and P-gp since it's a substrate of these proteins.
- A physiologically-based pharmacokinetic (PBPK) model of quinidine was developed to analyze how it absorbs, distributes, metabolizes, and is excreted in the body, also involving its metabolite, 3-hydroxyquinidine.
- The model demonstrated high accuracy, successfully simulating complex DDI scenarios with over 90% of predicted outcomes aligning closely with actual clinical data, and it will be made
Article Synopsis
- Tacrolimus, an immunosuppressant drug, is primarily metabolized by the enzymes CYP3A4 and CYP3A5, resulting in significant variability in how different individuals process the drug due to factors like food intake and genetic differences.
- The development of a whole-body pharmacokinetic model for tacrolimus using PK-Sim® allows researchers to predict how food-drug interactions and drug-drug interactions affect its pharmacokinetics.
- The model showed strong predictive capabilities, accurately aligning with observed data for both food and drug interactions, and has potential applications in improving drug discovery and personalized dosing strategies.