Clinical Pharmacology

DRUG METABOLISM & TRANSPORTERS

Most drugs are metabolised in the body before they are excreted.

This involves enzymatic oxidation or reduction (phase I metabolism) of a chemical group on the drug molecule, or the addition of an endogenous compound to the drug (phase II metabolism).  Metabolism usually results in the drug molecule becoming more polar, thus facilitating its removal from the body in the urine by the kidneys.  The enzymes responsible for metabolising drugs are mainly located in the liver. Identification of a drug’s metabolites is therefore important, as the pharmacological activity of a drug may be mediated to some extent by its metabolite.

The activity of any given enzyme can vary widely, as the regulation of enzyme expression is under both environmental and genetic control.  Interactions between co-administered drugs can also occur if drugs are metabolised by the same enzymes.  Using molecular biology techniques it is possible to identify individuals with altered function or expression of a particular enzyme.

Knowledge of the enzymes involved in the metabolism of a drug, and the kinetics of this reaction, allows one to predict if the drug will be subject to drug-drug interactions due to competition with other drugs for the enzymatic pathway, or if certain people will metabolise the drug differently to other people due to their genetics.
 

The Discipline of Pharmacology has extensive expertise in using purified enzyme preparations in vitro, obtained from tissues or expressed in cell lines, to identify the enzyme isoforms involved in drug metabolism and examine the kinetics of this process, and in the application of molecular biology techniques to identify people with genetic variations which result in altered function or expression of enzymes. It has a large liver tissue bank.

The senior researchers are:

Professor Andrew Somogyi
Dr Janet Coller
Dr Benedetta Sallustio

Specific Projects:
Effect of methadone on morphine glucuronidation

Identification of the CYP isoforms involved in the enantioselective metabolism of perhixiline - Betty Sallustio, Andrew Somogyi, Janet Coller