San Francisco Bay Area
Thesis: Develop mechanistic physiologically-based pharmacokinetic (PBPK) models to predict exposure and disposition of drugs and metabolites in various clinical scenarios and specific populations Research Mentor: Dr. Nina Isoherranen • Proficient at using different software packages, platforms, and tools including MATLAB, Simulink, Simbiology, R, GastroPlus, Simcyp, and Phoenix WinNonlin to conduct popPK, PKPD, and PBPK modeling • Designed, created, and optimized in silico novel and complex PBPK models to capture unique biological systems in special patient populations with different genetic, disease, and medication profiles • Measured, collected, assembled, and transformed physicochemical and pharmacokinetic data of drug molecules determined by in vitro and in vivo methods into in silico model parameter inputs • Integrated patient/system-specific parameters with drug-specific parameters to develop, verify, and optimize PBPK models to simulate drug dispositions in various special populations including liver and kidney disease patients, pregnant women, and children • Applied developed and verified mechanistic PBPK model to conduct in vitro to in vivo extrapolation (IVIVE), to enable reverse translation from clinical data to disease pathophysiology, to predict the magnitude of DDI, to quantify the impact of different physiological conditions and diseases on PK, and to inform the optimal design of future clinical studies
• Interpreted and transformed in vitro DMPK data including pH/biorelevant solvent-dependent solubility profile, time-dependent dissolution profile, permeability, and crystallization data to establish ACAT absorption models using GastroPlus • Verified and simulated PK profiles of a wide spectrum of compounds under both fasted and fed conditions to explore food effects • Identified substrate-dependent critical/sensitive parameters during drug absorption phase and significant mechanisms of food effects that could or couldn’t be captured by GastroPlus ACAT model • Assessed the overall applicability, strength, and limitation of GastroPlus to simulate food effect with respect to different BCS class compounds • Explored the potential utilization to use GastroPlus to facilitate the food effect clinical trial decision-making including dose selection, formulation selection, and number of subject calculation