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Genes determine drug dosage

  Thursday, 05 l 05 l 2011  Source:  Mind Your Body; The Straits Times   
By: Lee Hui Chieh

Genetic tests can help doctors decide how much of a drug to give. For instance, in 2007, the United States Food and Drug Administration required a label on warfarin, stating that users of this blood-thinning drug may respond differently to it depending on their genetic make-up. This is the result of work done by researchers at National University Cancer Institute, Singapore, who found that depending on which variants of two genes they have, people on warfarin need either a higher or lower dose.

One of the genes determines how well the body can metabolise warfarin, while the other – the one inhibited by warfarin – produces a substance that makes blood clot, said Dr Lee Soo Chin, one of the researchers and a senior consultant at the institute’s department of haematology-oncology. Not enough warfarin in patients who have had a heart attack, stroke or deep vein thrombosis could mean the risk of another blood clot and a repeat attack. But an overdose could cause bleeding, which could kill.

The team has devised a formula that calculates how much warfarin a patient needs, based on his weight, age and variants of the two genes. It is now conducting a study on 320 patients to compare the success of warfarin treatment in those whose dosages were calculated using the formula and those who got doses based on the conventional trial-and-error way.

Another researcher, Dr Goh Boon Cher, who heads the institute’s haematology-oncology department, said of the formula: “This would be a safer way of prescribing medication. If this works, in future, we could be using such tests for other drugs.” In fact, other researchers here are working on this. A National Cancer Centre Singapore team, led by Associate Professor Balram Chowbay, found that people with variants of a particular gene that are more common here than in Western countries had trouble breaking down the toxic by-product of a chemotherapy drug for colorectal and stomach cancer. In these people, the by-product accumulates, causing severe diarrhoea and lowering the count of infection-beating white blood cells. They need a lower dose of the drug irinotecan than the standard dose recommended for Caucasians, said Prof Balram.

The finding led the Health Sciences Authority to update the drug’s insert last year to recommend that a genetic test be done to check for variants of the gene before the drug is prescribed. The team is conducting a study to find the dosages for those with the variant genes.

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