?Understanding the pharmaco/nutrico/toxicokinetic behaviour of drugs, chemicals and food ingredients is a fundamental step in assessing the efficacy and safety of these materials. It can be challenging to study such substances directly in human subjects, while animal models lack direct translatability to humans due to inherent differences in species biology. One promising strategy is the use of physiologically-based pharmacokinetic (PBPK) modelling to predict the local tissue and systemic exposure of these substances. We have developed in-house in vitro and in silico tools to model chemical absorption, distribution, metabolism and excretion (ADME) in humans using data generated from in vitro assays. We apply these tools to predict pharmacokinetic profiles in different settings, ranging from oral or transdermal administration to studying special populations such as pregnant women, for a variety of substances including pharmaceuticals, food ingredients, environmental contaminants, essential micronutrients and microbial metabolites. These capabilities are further enhanced with state-of-the-art, enabling technologies such as the SHIME® intestinal digestion simulator and spatial mass spectrometry imaging.
The following tasks are expected of the candidate:
· Literature search to extract relevant ADME data for chemicals of interest
· Perform in vitro absorption, transporter, metabolism, fraction unbound and other related ADME assays
· Quantify membrane protein, metabolic enzyme and xenobiotic concentrations within biological samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS) instruments
· Integrate appropriate in vitro and in silico data into PBPK models to predict the ADME of chemicals
· Develop new and/or improve features of in-house models, including pharmacodynamic modelling
· Write scientific grant proposals, maintain laboratory notebooks, prepare scientific reports, presentations and manuscripts
· Supervise and train students and interns
Qualifications
· PhD in Pharmaceutical Science, Life Sciences or equivalent.
· Strong understanding of ADME and pharmacokinetic concepts is essential.
· Prior experience in in vitro ADME assays and analytical mass spectrometry workflows is desirable.
· Prior experience with PBPK tools such as Simcyp®, GastroplusTM, PK Sim, Matlab/Simbiology or other models is desirable.
· Able to work in a multi-disciplinary team, possess strong organizational and project management skills, demonstrate initiative and able to work independently.