Diploma Work, AstraZeneca, Gothenburg, 30hp

Title:
Preclinical Pharmacokinetic-Pharmacodynamic assessment of SGLT2 inhibitors

Background:
SGLT2 inhibitors is a class of drug compounds mainly reducing reabsorption of urinary glucose leading to sustained plasma glucose lowering. In addition to SGLT2 inhibitors being an effective anti-diabetic treatment they have also shown to have beneficial effects of to reduce clinical Heart Failure incidence and improved stabilisation of kidney glomerular filtration rate in CKD patients.

There are a number of pre-clinical pharmacological publications demonstrating beneficial effects of various SGLT2 inhibitors in animal models although these data have not been assessed systemically from a Pharmacokinetic-Pharmacodynamic relationship.

Aim:
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 SGLT2 inhibitors and secondly how they translate to clinical efficacy. This will be done by collecting available animal and human data for SGLT2 inhibitors, concerning their in vitro potency, efficacious in vivo concentrations and pharmacokinetics. The data will then be modelled to establish the PKPD (pharmacokinetic/pharmacodynamic) relationships between concentration and effect, and the correlation between compounds and cross-species will be investigated.

Requirements:
The student is expected to perform effective literature searches and read scientific articles on the topic.

The student is also expected to learn and perform basic modeling in the appropriate software (e.g. Phoenix WinNonlin).

The student is expected to be able to reason and discuss the implementation of possible translational correlations established in the work.

Last date to submit your application: 2017-05-07

For questions, please contact Rasmus Jansson Löfmark at AstraZeneca. Email: Rasmus.Jansson.Lofmark@astrazeneca.com