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Cough medicine could help doctors identify how breast cancer patients metabolize tamoxifen
Date:11/18/2010

ion and smoking.

Mrs de Graan and her colleagues at Erasmus studied the use of dextromethorphan, the active ingredient in cough suppressant medicine, in 40 breast cancer patients who had been taking tamoxifen for more than three weeks. Dextromethorphan is metabolised in the same way as tamoxifen and is harmless to the patient. "It is a so-called 'probe' drug, a harmless substance that can be used to predict the metabolism of another drug. We used dextromethorphan to evaluate its use as a probe drug for tamoxifen metabolism," she said.

The researchers gave their patients 30mg of dextromethorphan as liquid cough syrup and then asked them to take their oral tamoxifen two hours later. Over the next 24 hours they took different blood samples to measure both dextromethorphan and tamoxifen metabolites, and then calculated how well dextromethorphan metabolism predicted and correlated with tamoxifen metabolism.

"We found that dextromethorphan is a very good way to predict endoxifen concentrations," said Mrs de Graan. One patient was taking the anti-depressant, paroxetine, which is known to inhibit CYP2D6, and the dextromethorphan probe accurately predicted the resulting lower concentrations of endoxifen.

Measuring dextromethorphan is easier than measuring levels of the metabolite endoxifen and, in addition, it can be applied to other compounds that are metabolised by CYP2D6 and CYP3A.

"Tamoxifen is prescribed to women for as much as five years in the adjuvant setting, so it is highly important to know beforehand if the therapy is going to be effective. When it is known that a woman metabolises tamoxifen poorly, a switch in drugs or an increase in dose can be considered. Looking at a patient's genetic make-up (genotyping) is one possible way to predict the metabolism of an individual patient, but it only looks at one gene for one enzyme involved in the metabolism of tamoxifen: CYP2D6. However, tamoxifen is also metabolised by anoth
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Contact: Emma Mason
wordmason@mac.om
ECCO-the European CanCer Organisation
Source:Eurekalert

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