Publications by authors named "P Vaddady"
Article Synopsis
- This study evaluated the pharmacokinetics (PK) of quizartinib and its metabolite AC886 in newly diagnosed FLT3-ITD-positive acute myeloid leukemia (AML) patients receiving standard chemotherapy, using data from the Phase 3 QuANTUM-First trial and earlier studies.
- The PK of quizartinib was modeled as a three-compartment system, while AC886 followed a two-compartment model, both showing significant variability among individuals.
- The research also identified the influence of CYP3A inhibitors on drug exposure, revealing a need for dose adjustments and noting differences in quizartinib exposure across treatment phases compared to previously studied patient groups.
Article Synopsis
- Quizartinib extends the QT interval by inhibiting a specific potassium current, and its effects were studied in newly diagnosed acute myeloid leukemia (AML) patients using complex modeling techniques during a clinical trial.
- The research evaluated how quizartinib and its metabolite AC886 impact the Fridericia-corrected QT interval (QTcF) using multiple measurements and various modeling approaches, identifying factors like age and hypokalaemia as relevant.
- Results showed a significant non-linear increase in QTcF with higher quizartinib doses, supporting the need for dosage adjustments in patients, especially when combined with certain other medications.
Within-chain parallelization-Giving Stan Jet Fuel for population modeling in pharmacometrics.
CPT Pharmacometrics Syst Pharmacol
January 2025
Stan is a powerful probabilistic programming language designed mainly for Bayesian data analysis. Torsten is a collection of Stan functions that handles the events (e.g.
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- The landscape of oncology drug development has improved significantly, leading to better patient outcomes and quality of life, particularly through initiatives like Project Optimus by the FDA.
- Project Optimus aims to reform how drug doses are selected in oncology, shifting the focus from maximum tolerated doses to more personalized strategies that consider disease and patient specifics.
- The Oncology Dose Optimization IQ Working Group emphasizes the need for a tailored, evidence-based approach to dose optimization, acknowledging industry's challenges and advocating for strategies that adapt to various factors in cancer treatment.
Application of the model-informed drug development paradigm to datopotamab deruxtecan dose selection for late-stage development.
CPT Pharmacometrics Syst Pharmacol
January 2024
To replace the conventional maximum tolerated dose (MTD) approach, a paradigm for dose optimization and dose selection that relies on model-informed drug development (MIDD) approaches has been proposed in oncology. Here, we report our application of an MIDD approach during phase I to inform dose selection for the late-stage development of datopotamab deruxtecan (Dato-DXd). Dato-DXd is a TROP2-directed antibody-drug conjugate being developed for advanced/metastatic non-small cell lung cancer (NSCLC) and other tumors.
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