Fluoride Action Network

Fluorourocil: Catheter studies raise acid alert

June 8th, 2015 | By Anna Demming, Online editor
Location: International
Industry type: Pharmaceuticals

Chemotherapy treatments routinely deliver drugs via catheters, yet in 25% of these catheters there are complications that are generally not well understood. For the first time researchers have studied the behaviour of a common chemotherapy drug on silver, which is often used to coat catheters and other apparatus used in chemotherapy drug delivery. The studies reveal an alarming level of reactivity between the medicine fluorourocil and silver at body temperature. This could lead to the release of hydrofluoric acid, which could damage the catheter and harm the patient. Studies of the same drug on graphene coatings suggest they would provide a safer alternative.

“Out of all of the materials that chemotherapy drugs are exposed to, we chose to look at silver first because we thought we might get a reaction, so we weren’t surprised when we did,” says Justin Wells, a surface science researcher at the Norwegian University of Science and Technology. “What was surprising was how much.” Silver catalyses the decomposition of fluorourocil at just the wrong level of reactivity – if it were more reactive the decomposing drug might stick to the silver surface and inhibit further chemistry. However the rate of the reaction at body temperature decomposes the fluorourocil while leaving the surface free for further reactions.

When in solution, the hydrogen fluoride formed is a highly corrosive acid. Not only could it damage the catheter, but if it entered the bloodstream of the patient it would be acutely poisonous. The use of silver as a protective coating inside catheters is relatively new; it has been noted that the silver disappears very quickly, which these latest results may explain. “If you wanted to remove a metal coating a strong acid would be a good way to go about it,” Wells says.

… At room temperature the decomposition of fluorourocil on silver was so fast that the dynamics of the reaction were lost, so the researchers cooled the system to -170 °C before slowly raising the temperature to body temperature. Looking for reactions that might occur in the human body at such low temperatures might seem strange, particularly from a clinical point of view. However it made sense to the team of surface physicists as it allowed them to see how the reactions proceeded.

Starting at low temperatures also helped control the experimental conditions. Preventing the x-ray gun from sparking requires a high vacuum, but the fluorouracil has a high vapour pressure, which makes an ultra-high vacuum hard to sustain. Beginning the experiment at lower temperatures made it easier to maintain the ultra-high vacuum.

Comparing the results with calculations by computational chemists confirmed the team’s findings. The calculations showed the likely reaction pathways and the energy required for the different steps, which was consistent with the temperature dependence of the reaction that the team had observed…

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From Wikipedia: Prescription drug

Fluorouracil or 5-FU is a drug that is a pyrimidine analog which is used in the treatment of cancer. It is a suicide inhibitor and works through irreversible inhibition of thymidylate synthase. It belongs to the family of drugs called the antimetabolites.[2]It is on the World Health Organization’s List of Essential Medicines, a list of the most important medications needed in a basic health system.[3]