Physiologically Based Pharmacokinetic Modelling for the Optimisation of Complex Clinical Scenario in Elderly Individuals

Research project: The efficacy and toxicity of pharmacological strategies can be complicated by a broad variety of factors including patient characteristics such as age and co-morbidities. Older individuals are prone to multi-morbidities, hence polypharmacy and consequently have higher probability of drug–drug interactions (DDIs). DDI can be defined as the modulation of the pharmacologic activity of one drug by the prior or concomitant administration of another drug. DDI can jeopardise the clinical management of multiple therapies and complicate the prescription of treatments. Adverse drug reactions caused by DDIs can represent more than 20% of all reported side effects.

Elderly patients are often excluded from clinical trials and knowledge about pharmacokinetics and DDIs magnitudes is sparse. Due to the high number of possible drug combinations comparatively few DDI studies are conducted therefore there is no guidance on how to handle DDIs in this population of patients. The aim of this project is to utilise advanced experimental and mathematical tools for the simulation of relevant clinical scenario, supporting the prediction of DDI magnitude and relative risks in elderly patients. Innovative lab and computer-based approaches will be integrated to provide a pharmacokinetic and pharmacodynamic evaluation of DDIs and support the simulation of strategies to rationalise the prescription of complex therapies in elderly patients. The research activity will focus on key therapeutic areas such as anti-infectives cancer drugs, calcium channel inhibitors, beta blockers, anticoagulants/antiplatelets, anticonvulsants, contraceptives, hypnotics/anxiolytics, corticosteroids and antipsychotics.

For more details on the research project please contact the supervisors:
Dr Marco Siccardi (Molecular and Clinical Pharmacology) [Email Address Removed]
Professor Rachel Bearon (Mathematical Sciences) [Email Address Removed]

Please apply by sending CV and letter of application to Ms Diane Ashton [Email Address Removed]

Training: The University of Liverpool is setting up a Doctoral Network in Technologies for Healthy Ageing to train the next generation of physical scientists and engineers to develop novel technologies and devices to address the challenges faced by older people and our clinical colleagues who work with them. It is structured around three healthy ageing challenges; prolonging independence, maintaining wellness and accelerating recovery.

All students will undertake a specific training programme in conjunction with their research project. A range of training modules have been designed to provide the student cohort with the high levels of scientific knowledge and engineering expertise needed for research and development of devices and technologies appropriate for the Healthy Ageing agenda. Through this approach our students will learn skills that will provide them with a unique advantage to develop technologies appropriate for this community and significantly enhance their employability in this emerging field. At the start of the programme students will have a masterclass session with a consultant in clinical geriatric medicine, a therapist and a social worker to introduce them to the challenges of the older person in the community through case studies. Each student will spend a week with a Consultant Geriatrician in clinics and community visits. This clinician will remain in contact with the student throughout their PhD in the role of a mentor to maintain the interface between their projects and the healthcare challenges. Innovative training sessions will ensure the training and research is grounded in real world challenges and have been constructed to provide Essential Transferable Skills and Subject Broadening Skills. The student will be a member of the Liverpool Doctoral College which provides further training opportunities over all three years of the PGR programme, and includes Inductions (general and safety), E-learning (e.g. Good Research Practice), seminars (presenting as well as attending), outreach opportunities and journal clubs.