A common anti-psychotic drug used to treat schizophrenia and bipolar disorder will come under the microscope as part of a new internationally-funded study led by researchers from Flinders University.
A research team from the Department of Clinical Pharmacology, led by Dr Andrew Rowland and Dr Tom Polasek, has just received a $160,000 grant from UK-based company Simcyp to investigate whether computer modelling software can be used to predict dosing of the drug olanzapine.
Olanzapine is widely used in the treatment of schizophrenia, acute mania and bipolar disorder, yet up to 80 per cent of patients stop using it within five years because of the way the body reacts to the drug – by either getting rid of it so quickly that it has no therapeutic effect or by not getting rid of it, causing the drug to build-up to toxic levels.
“Whenever a person takes a drug two things happen – the drug does something to the body and the body does something to the drug, and that’s to get rid of it,” Dr Rowland said.
“But with olanzapine, the enzyme in the body that’s involved in getting rid of the drug works differently in different people and because of this it’s hard for doctors to know what dose to prescribe,” he said.
“So at the moment doctors give a standard dose and in some people the enzyme doesn’t work properly to get rid of it so they develop toxicity, which leads to nausea, vomiting and basically they stop taking the drug because it makes them feel so sick.
“For other people, the body gets rid of it so quickly that it doesn’t have a chance to work so they stop taking the drug because, obviously, it’s not working.”
Dr Rowland said the study would explore whether a computer program (Simcyp) that is traditionally used by drug companies to predict “clearance” rates for new drugs – meaning how quickly people take to eliminate the drug from the body – could be used by clinicians to find the best dose of olanzapine for individual patients.
“Using samples from human liver tissue we’ll work out how clearance occurs, so how quickly it goes through the body, and from there we’ll measure enzyme activity in 100 people who are already taking olanzapine,” he said.
“The ultimate goal is to demonstrate that the Simcyp software can predict how olanzapine can be cleared so that, for example, a doctor could check the patient’s enzyme activity using a quick, safe and simple test and give the patient the most appropriate dose.
“At the moment therapeutic drug monitoring for olanzapine is poorly utilised so a simple, rapid and non-invasive approach to support clinicians to tailor dosage is needed.”
Dr Rowland said dose individualisation was the “holy grail” of pharmacology, and that once researchers knew how to correctly dose olanzapine the same method could be applied to other drugs.
As an early career researcher, he said it was a “great honour” to win the first ever Simcyp grant.
“It highlights how the Department of Clinical Pharmacology at Flinders University is held in high regard internationally, and it builds on the department’s strong reputation.”
The two-year study will be carried out by Drs Rowland and Polasek and Flinders postdoctoral researcher Porntipa Korprasertthworn, in collaboration with researchers from the University of Sydney and the University of Queensland.