title: Advances in drug metabolism and pharmacogenetics research in Australia.
abstract: Metabolism facilitates the elimination, detoxification and excretion in urine or bile (as biotransformation products) of a myriad of structurally diverse drugs and other chemicals. The metabolism of drugs, non-drug xenobiotics and many endogenous compounds is catalyzed by families of drug metabolizing enzymes (DMEs). These include the hemoprotein-containing cytochromes P450, which function predominantly as monooxygenases, and conjugation enzymes that transfer a sugar, sulfate, acetate or glutathione moiety to substrates containing a suitable acceptor functional group. Drug and chemical metabolism, especially the enzymes that catalyse these reactions, has been the research focus of several groups in Australia for over four decades. In this review, we highlight the role of recent and current drug metabolism research in Australia, including elucidation of the structure and function of enzymes from the various DME families, factors that modulate enzyme activity in humans (e.g. drug-drug interactions, gene expression and genetic polymorphism) and the application of in vitro approaches for the prediction of drug metabolism parameters in humans, along with the broader pharmacological/clinical pharmacological and toxicological significance of drug metabolism and DMEs and their relevance to drug discovery and development, and to clinical practice.
authors.affiliation: Department of Clinical Pharmacology, Flinders University School of Medicine and Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Bedford Park, South Australia, Australia. Electronic address: Peter.Mackenzie@flinders.edu.au.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Mackenzie
authors.affiliation: Department of Pharmacology, School of Medicine, Adelaide University, South Australia, Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Somogyi
authors.affiliation: Department of Clinical Pharmacology, Flinders University School of Medicine and Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: John O
authors.initials: JO
authors.lastname: Miners
mesh_terms: D000818:Animals; D001315:Australia; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D055808:Drug Discovery; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Drug metabolism; Glutathione transferase; N-acetyltransferase; Pharmacogenetics; Sulfotransferase; UDP-glycosyltransferase