Development Of A Pharmacokinetic (Pk) Model And Assessment Of Patient (Pt) Covariate Effects On Dose-Dependent Pk Following Different Dosing Schedules In Two Phase I Trials Of Ap23573 (Ap), An Mtor Inhibitor

Authors: Desai AA, Mita M, Fetterly GJ, Chang C, Netsch M, Knowles HL, Bedrosian CL, Rowinsky E, Tolcher A, Ratain MJ
Conference: ASCO
Keywords: antineoplastics, body surface area, BSA, cancer, dose, dose-limiting toxicity, maximum tolerated dose, MTD, mucositis, Oncology, RBC, red blood cell, safety, WinNonlin
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background

AP23573 is a novel non-prodrug rapamycin analog that potently inhibits mTOR (through bivalent binding to FKBP and mTOR), a downstream effector of PI3K/Akt and nutrient-sensing pathways. A PK model was developed to characterize the blood concentration-time profile of AP23573 and evaluate patient covariate effects following different dosing schedules.

American Society of Clinical Oncology (ASCO), Orlando, Florida, May 2005

By A.A. Desai, M. Mita, G.J. Fetterly, C. Chang, M. Netsch, H.L. Knowles, C.L. Bedrosian, E.Rowinsky, A. Tolcher, M.J. Ratain