Development of a Modeling Framework to Simulate Efficacy Endpoints for Motesanib in Thyroid Cancer Patients

To develop a modeling framework that simulates clinical endpoints (objective response rate and progression-free survival) to support development of motesanib. The framework was evaluated using results from a phase 2 study of motesanib in thyroid cancer. Models of probability and duration of dose modifications and overall survival were developed using data from 93 patients with … Continued

Population Pharmacokinetic/Pharmacodynamic Modeling for the Time Course of Tumor Shrinkage by Motesanib in Thyroid Cancer Patients

To develop a population pharmacokinetic/pharmacodynamic model describing the relationship between motesanib exposure and tumor response in a phase 2 study of motesanib in patients with advanced differentiated thyroid cancer or medullary thyroid cancer. Data from patients (n = 184) who received motesanib 125 mg once daily were used for population pharmacokinetic/pharmacodynamic modeling. Motesanib concentrations were … Continued

Quantitative Structure–property Relationships of Camptothecins in Humans

The purpose of this study was to develop quantitative structure property relationships (QSPR) for the pharmacokinetics and the susceptibility to BCRP-mediated efflux of ten drugs in the camptothecin family of topoisomerase I inhibitors. Pharmacokinetic parameters (total and lactone clearance, total steady-state volume of distribution, and lactone:total area under the curve ratio) and IC50 values of … Continued

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