PhD Studentship in Pharmacokinetic/Pharmacodynamic Modelling, University of Nottingham

Reference

MED1068

Job Type

Research & Teaching

Department

School of Veterinary Medicine & Science

Pharmacokinetic/Pharmacodynamic modelling of animal data to predict optimal drug dosing regimens in humans

Principal supervisor:
Dr Stuart Paine (School of Veterinary Medicine and Science) email: stuart.paine@nottingham.ac.uk

Dr Cyril Rauch (School of Veterinary Medicine and Science)
Peter Littlewood (Vertex Pharmaceuticals Ltd)

The School of Veterinary Medicine and Science at the University of Nottingham is the first brand new, purpose-built veterinary school in the UK for over 50 years and it is our intent to make significant leading contributions to both veterinary research and teaching within the context of valid relevance and application to the wider veterinary profession.

Research is central to the activities of the School, both in terms of maintaining ourselves at the forefront of national and international efforts in veterinary medicine but also as an integral part of the training and education for undergraduate and postgraduate students.  In the 2008 Research Assessment Exercise, the School of Veterinary Medicine and Science joint submission with the School of Biosciences was ranked first in the country for the power of its research with 95% of its activities classified at an international standard.

A simple definition of pharmacokinetics (PK) is "how the body processes a drug", resulting in a drug concentration in the body. Pharmacodynamics (PD) can similarly be defined as "how the drug acts on the body", resulting in a measurable drug effect. Combining these two ideas leads to the concept of dose-concentration-effect, which can be modelled using PK/PD modelling. The result of such modelling is a mathematical description of a drug's fate in the body, for an individual. The application and understanding of PK/PD models in animals allows a better understanding of the optimal dosing regimens for the use of the specific drug in that species. Moreover, established PK/PD models in small species allow the extrapolation of PK/PD modelling to larger species including man using allometric methods. Thus, a PK/PD model in mouse can be used to predict the outcome of both the pharmacokinetics and pharmacodynamics within a human clinical trial. Understanding species differences in PK/PD can be investigated by firstly understanding species differences from drug metabolising in vitro systems such hepatocytes, microsomes and recombinant metabolising enzymes. The enzyme kinetics from each species can be scaled up to blood PK using physiological based PK (PBPK) modelling. This also allows the prediction of harmful/beneficial drug-drug interactions from enzyme inhibition studies using mathematical modelling.

The objectives of this project are to use PK/PD understanding to relate drugs levels in animal models to an efficacious endpoint using mathematical models. This may lead to a mechanistic understanding of the mode of action of the drug. The mathematical modelling will be used to analyse enzyme kinetics and inhibition, PK, physiological based PK, population PK and PK/PD.

The project proposal involves a multidisciplinary approach ranging from mathematical modelling to physiology. A successful outcome would allow greater benefit to the welfare of animals and humans through new dosing regimens and advise the pharmaceutical industry on the potential for drug-drug interactions and first time in man studies of new chemical entities (NCEs).

The PhD studentship would involve the prospective student spending 6 months at Vertex Pharmacueticals Ltd at their Oxford site.

Students should have a minimum of a 2.1 undergraduate degree or a minimum of a 2.2 degree and a masters degree in either physical science, mathematics or engineering subjects. Candidates will be happily considered from other subject areas but will require either strong mathematical skills or experience with kinetic modelling.

The studentship is available for a period of three years from August 2012 and provides the standard UK/EU postgraduate stipend, though there are potential funding restrictions for non-EU students.

Informal enquiries may be addressed to the principal supervisor: Dr Stuart Paine, email: stuart.paine@nottingham.ac.uk.

Students should apply online via https://pgapps.nottingham.ac.uk and include a cv, names of 2 references and details of degree and module results.  Any queries regarding the application process should be addressed to Helena Percival, Postgraduate Admissions Officer, (email: postgrad-vet@Nottingham.ac.uk). The position will be filled when suitable candidates have been identified. Early application is strongly encouraged.

• Information for candidates ( pdf | doc )
• Apply Online