Population-based pharmacokinetic-pharmacodynamic modelling
Population modelling methods provide a tool for integrating information about drug disposition and action across data sets (pre-clinical, Phase I, Phase II and Phase III) while explaining under lying mechanisms and quantitating between and within subject variability. It is a widely used method in drug development that has the potential to maximise efficiency by increased understanding of the available data, and informed design of new studies. We have had extensive experience with this method in academia and industry.
Physiologically-based pharmacokinetic modelling
Empirical compartmental models are commonly used to describe the pharmacokinetics of drugs. However, these models do not always represent the interaction between physiology and drug disposition. Physiologically based pharmacokinetic models seek to address this deficiency, by represent drug kinetics in one or more "real" organs and describe "whole body" kinetics by joining together sub-models with drug transport by blood flow as dictated by anatomy. We have employed physiologically based pharmacokinetic analyses in a range of areas, authored book chapters and tutorial papers, and delivered workshops at conferences in this area.
While modelling and simulation is increasingly becoming commonplace in the understanding human health and pharmacotherapy, this is not yet the case for veterinary research. This has lead to recent calls in the veterinary literature to address this deficit and apply pharmacometric analyses to advance the welfare of animals. We currently have several collaborations with the University of Sydney faculty of Veterinary Science and a commercial partner in the areas of antifungal and cardio-active drugs.
For more information, contact Dr David Foster
Rheumatoid arthritis, Osteoarthritis and gout
This research involves developing methodologies and techniques that use differences between patients to predict differences in drug concentration, efficacy and toxicity, including patient age, gender, body weight, inherited (genetic) differences, concurrent diseases and environmental exposures. Ultimately, this research intends to provide guidance to prescribers regarding what the safest and most effective medicine is for a patient, and also regarding what dose will strike the most appropriate balance between likelihood of efficacy and risk of toxicity..
Improving our understanding of pain and its treatment
Pain and its perception is a complex process, with many factors contributing to wide variability between people. Our group has a long history of applying modelling and simulation techniques to better understand the pharmacokinetics and pharmacodynamic (both desirable and undesirable) effects of opioid drugs and their impact on pain. Our work spans modelling using conventional and physiologically-based pharmacokinetic analyses for a range of opioid drugs, and linking these to effects ranging from analgesia to EEG evoked potentials. This work is underpinned through a long-standing collaboration with the University of Copenhagen, and more recently with the University of Cape Town.
Therapeutic Drug Monitoring and Bayesian forecasting
Therapeutic drug monitoring (TDM) uses measured drug concentrations with clinical interpretation to adjust dosing regimens. However, for some drugs the complex relationship between pharmacokinetics and individual patient factors, interpreting and deciding upon the appropriate regimen is often not straightforward. Bayesian forecasting provides a mathematical method for selecting a dose regimen by considering previous experience (“the prior”) and observations (“the new data”), where the prior is structured in the form of a population pharmacokinetic and/or pharmacodynamic model, thus removing much of the “guess work”.
Differences between patients or with a patient over time in the absorption of drugs is often an important cause variability in response to drugs. This variability can be caused by differences between patients in gastrointestinal physiology, such as gastric motility and pH, or even consumption of different foods. Our group employs population-based pharmacokinetic analyses including linking in vitro dissolution data to in vivo plasma concentration data to better characterise the key features that affect oral drug absorption.
Development of innovative professional services to extend the roles of pharmacists
My major research interest is in the area of substance dependence with a particular emphasis on opioids. My pharmacy practice research is currently focussed on the development of innovative professional services to extend the roles of pharmacists in a financially-pressured health care system.
For more information, contact Dr Libby Hotham
Medicine adherence and impact of de-prescribing on the disposition and response to various medicines
All registered drugs available in Australia undergo rigorous examination prior to being made broadly available, but many of these investigations have been conducted in younger individuals who take few other medicines and have few other concurrent diseases. This is not usually how these medicines are used when they are commonly prescribed. Our research involves examining the effects of common diseases on the pharmacokinetics of medicines when they are prescribed to older individuals, and may help to explain why older individuals experience more side effects from prescription medicines. It is also well described that many medicines are started and ceased over a relatively short time period in elderly individuals. Elderly individuals are more susceptible to potentially harmful drug-drug interactions, and changes to medicines may substantially affect the concentrations of other medicines that the patient is taking, potentially leading to either therapy failure or, of more concern, life-threatening side effects.
Clinical and Regulatory Therapeutics and Toxicology
This work is funded by an NHMRC Program Grant and 2x FDA grants and is undertaken jointly with University of Queensland (insert web link), The University of Sydney (insert Monika’s web link), the University of Newcastle, UCF, San Francisco USA, FDA Washington DC USA, Goethe-Universitäte Frankfurt Germany.
This work is concerned with the safety for patients who have been exposed to environmental, occupational, consumer medications or poisons. A key focus of this work is on understanding the behaviour and effects of these agents in the body and better management strategies for these patients. UniSA provides the core analytical service for poisonings both in SE Asia and in Australia and in providing mechanistic toxicology studies.
Work with the FDA is concerned with a better understanding of the determinants of topical product absorption and effects for the various products that are now on the market and those that with to enter the market.
Key personnel involved in this work are Professor Michael Roberts, Dr Lorraine Mackenzie, Tom Robertson, Dr Ahmed Abdalla, Ms Kushari Burns, Dr Amy Holmes, Dr Oleksandr Chernyavskiy.
For further information please contact Dr Lorraine Mackenzie
Targeted Drug, Nanoscience and Biological Technology Formulation Delivery, Effect and Safety
This work involves:
- Developing formulations for cosmeceutics and therapeutic delivery
- Selective nanomaterial topical efficacy and safety
- Systemic disposition and effects of drugs, poisons, nanosystems and biologicals
- Environmental, physiological genomic and pathological determinants of effect and safety.
Key personnel involved in this work are Professor Michael Roberts, Dr Lorraine Mackenzie, Dr Amy Holmes, Dr Azadeh Alinaghi, Dr Michael Pastore, Dr Maryam Nakhjavani, Dr Oleksandr Chernyavskiy and Dr Lydia Sandiford
For further information please contact Dr Lorraine Mackenzie
Exploring the effect of age, other diseases and other medicines on the Pharmacokinetics of Medicines
All registered drugs available in Australia undergo rigorous examination prior to being made broadly available, but many of these investigations have been conducted in younger individuals who take few other medicines and have few other concurrent diseases. This is not usually how these medicines are used when they are commonly prescribed. This research involves examining the effects of common diseases on the pharmacokinetics of medicines when they are prescribed to older individuals, and may help to explain why older individuals experience more side effects from prescription medicines. The results of the research also aims to provide evidence to support the most appropriate drug selection and dose regimen for older adults.
Pharmacokinetic Data Analysis: Pre-Clinical Studies and Clinical Trials
The success of a drug in development is based on its profile in three primary, inter-connected areas: pharmacokinetics, pharmacodynamics and clinical outcomes. The clinical outcomes of a drug are perhaps the most important, with the balance between the drug’s ability the treat the disease/condition whilst maintaining a low incidence of side effects critical to its success in practice. However, this is largely influenced by how the drug interacts with the body’s biological processes (i.e. pharmacodynamics) which is in turn affected by the movement of the drug into, through and out of the body (i.e. pharmacokinetics). An understanding of drug pharmacokinetic properties therefore plays a key role in the selection of treatment strategies for the optimisation of these processes. Bringing extensive expertise in both academic and industry settings, our group uses model dependent (compartmental) and independent (non-compartmental) individual and population pharmacokinetic analyses to determine drug exposure from which factors such as first-in-human dose determination, dose regimen selection and bioequivalence assessments can be made.
Improving the Therapeutic Use of Anti-Infective and Chemotherapeutic Agents
There are no fields of medicine in which the individualisation of medications is more important than in the areas of infectious diseases and oncology. In both cases, effective clinical management requires the right dose, at the right time, in the right patient in order to maximise therapeutic and biological outcomes and minimise adverse drug reactions. For the most part, dosing of these drugs is empirical, and although simple strategies are implemented in clinical practice for dose modification (based on renal function, weight, age, etc.), a more comprehensive understanding of the actions of these drugs is needed in order to develop the most appropriate treatment regimens for the best therapeutic outcomes. Utilising pharmacokinetic modelling and simulation, our group’s research focusses on addressing the medication issues in these therapeutic areas and providing an evidence-based approach to the appropriate prescription and management of these drugs in clinical practice.
Regulation and Optimal Clinical Use of Biologic Medicines
With the advent of the biologic medicine era, and the subsequent arrival of biosimilars, considerable opportunities have emerged for the effective treatment of some diseases for which previous therapeutic options were limited or inadequate. However, this had also raised complex regulatory issues and significant pharmacoeconomic concerns. Combining expertise in pharmacology, modelling & simulation and therapeutics, our group has a specific interest in the complexities surrounding the regulation of biologics and biosimilars, as well as the application of pharmacologic principles to improve the cost-effectiveness and therapeutic use of these drugs in clinical practice.
Areas of study and research
- Health Research
- Alliance for Research in Exercise, Nutrition and Activity (ARENA)
- Centre for Cancer Biology
- Centre for Drug Discovery and Development
- Centre for Population Health Research
- Centre of Research Excellence for the Prevention of Chronic Conditions in Rural and Remote High Risk Populations
- International Centre for Allied Health Evidence
- Medicine and Device Surveillance CRE
- Quality Use of Medicines and Pharmacy Research Centre
and Social Sciences
- Art, Architecture and Design
- Communication, International Studies and Languages
- Psychology, Social Work and Social Policy
- Hawke Research Institute
- Asia Pacific Centre for Work Health and Safety
- Australian Centre for Child Protection
- Barbara Hardy Institute
- Centre for Research in Education
- Hawke EU Jean Monnet Centre of Excellence
- Centre for Islamic Thought and Education
- International Centre for Muslim and non-Muslim Understanding
- Research Centre for Languages and Cultures
- Zero Waste SA Research Centre for Sustainable Design and Behaviour (sd+b)
IT, Engineering and
- Future Industries Institute
- UniSA College