Quantitative In Vitro-in Vivo Extrapolation: Realising The Promise
Funder
National Health and Medical Research Council
Funding Amount
$529,509.00
Summary
Most drugs are 'broken down', or metabolised, in the body by enzymes which are located mainly in liver. Knowing the efficiency of drug metabolism in patients is important for the discovery of new drugs and for the rational use of established drugs. This project will develop in vitro, or test-tube, approaches that predict how well a drug is metabolised in humans and whether it will interact with coadminsitered drugs. In turn, this allows prediction of drug dosage and frequency of administration.
Novel Cellular Trafficking Mechanisms For The Drug Influx Transporter, Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in indivi ....Human organic anion transporting polypeptides (OATPs) are membrane proteins that regulate the cellular uptake of endogenous and exogenous substances including anti-cancer drugs. OATPs strongly determine whether such drugs enter the tissues where they are required to exert their effects. This project will study novel mechanisms that we have recently identified that determine the orientation of transporters in the cells. These processes can be impaired by a common pharmacogenetic variant in individuals.Read moreRead less
Pharmacokinetic And Pharmacodynamic Studies Of The Newer Immunosuppressants
Funder
National Health and Medical Research Council
Funding Amount
$406,650.00
Summary
After an organ transplant (such as a liver or kidney transplant), people need to take medicines continually to stop their immune systems from rejecting their new organ. This treatment with immunosuppressant drugs is vital for long-term success of the graft. These drugs are designed to prevent rejection in patients who have received organ transplants (e.g. kidney, liver) and are also being used to treat a variety of autoimmune diseases, including rheumatoid arthritis. However, too many people are ....After an organ transplant (such as a liver or kidney transplant), people need to take medicines continually to stop their immune systems from rejecting their new organ. This treatment with immunosuppressant drugs is vital for long-term success of the graft. These drugs are designed to prevent rejection in patients who have received organ transplants (e.g. kidney, liver) and are also being used to treat a variety of autoimmune diseases, including rheumatoid arthritis. However, too many people are losing transplanted organs, or not achieving remission from their autoimmune diseases, or are experiencing significant illness and sometimes death from over immunosuppression (infection or side effects) because these drugs are not being used in the best way. The quality and duration of life of increasing numbers of Australians is being affected by lack of understanding and application of some basic principles about dosing regimens for these drugs. The aim of this project is to accurately define the best way to dose these newer immunosuppressant drugs in Australian populations, before they become more widely used .Read moreRead less
Drugs are broken down in the body by the process of metabolism. Metabolism is important as both a detoxification and elimination mechanism, and determines dose rate for chronically administered drugs. Many drugs are metabolised by a reaction called glucuronidation. We will characterise the various components of the glucuronidation reaction in an integrated manner in order to understand and predict factors that influence an individual's capacity to metabolise drugs and other chemicals.
Improving The Use Of Chemotherapy By Targeting The Inflammatory Response
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Patient differences in clearance of anti-cancer drugs have a major impact on the success of chemotherapy. Benefit is lost if the drug is cleared too rapidly, while slow elimination causes toxicity. We will use well characterised mouse models that mirror the human situation to study the causes and effects of reduced drug metabolism in cancer. The data will guide future human studies that will result in improved diagnostic and therapeutic interventions to improve the tolerance of chemotherapy.
Predicting Drug-drug Interactions Due To Tyrosine Kinase Inhibitors: Inhibition Of Drug Metabolising Enzymes And Transporters
Funder
National Health and Medical Research Council
Funding Amount
$535,495.00
Summary
Tyrosine kinase inhibitors (TKIs) are a new class of anticancer agents. Cancer patients typically receive multiple drugs, for the treatment of cancer and other diseases, increasing the probability of interactions between coadministered drugs. Despite the widespread use of TKIs, their potential to cause drug interactions is poorly understood. Using novel in vitro approaches, this project will identify drug interactions precipitated by TKIs thereby improving drug efficacy and patient safety.