Translation of drug-induced effects on NASH from mouse to human using pharmacokinetic-pharmacodynamic modelling
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. AstraZeneca is proud to offer a unique workplace culture that inspires innovation and collaboration. Co-workers are empowered to express diverse perspectives - and are made to feel valued, energized and rewarded for their ideas and creativity.
We are looking for a student for the start of a thesis work in August. You will be part of Innovative Medicine Unit, Cardiovascular, Renal and Metabolic Disease, DMPK. The DMPK department is accountable for delivering integrated drug dispositions, biotransformation and pharmacokinetics input to projects from target selection through to lifecycle management as well as for pre-clinical translational PK/PD with the aim of predicting a safe and efficacious dose in human. The thesis work is to be conducted during the period 26/08/2018 – 10/01/2019.
Non-alcoholic steatohepatitis (NASH) is a growing disease, closely linked to obesity and type 2 diabetes. It involves steatosis (fatty liver), inflammation and fibrosis (scarring) of the liver, and ultimately need for liver transplantation. Currently no treatments have been approved for NASH, while many are currently under development across pharma. Diet-induced obesity (DIO) mouse models are used to evaluate drug-induced effects on NASH, however, the quantitative translation between these effects and the corresponding effects on humans has not been assessed systematically.
The objective is to assess the public pharmacology data from an exposure-response relationship / Pharmacokinetic-Pharmacodynamic relationship how these effects in animal models translate cross different drugs and to clinical efficacy. This will be done by collecting available animal and human data for drugs with effects on NASH, concerning their in vitro potency, efficacious in vivo concentrations, pharmacokinetics and pharmacodynamics. The data will then be modelled to establish the PKPD (pharmacokinetic/pharmacodynamic) relationships between concentration and effect, and the correlation
You are currently pursuing a Master’s degree in biomedicine, pharmacy, biotechnology or equivalent.
To succeed in this Thesis work you will need to
You should have an analytical and scientific mindset, driven by curiosity and ambition to learn. You will perform effective literature searches and read scientific articles on the topic. You are also expected to learn and perform basic modeling in the appropriate software (e.g. Phoenix WinNonlin). Moreover, you are expected to be able to communicate your work in different kinds of presentations as well as reason and discuss the implementation of possible translational correlations established in the work.
For enquiries and more information regarding the project call Linnéa Bergenholm at 031-776 10 15 or send an email to Linnea.Bergenholm@astrazeneca.com
Welcome with your application including your CV and personal letter, no later than 1st of June.