New test can flag drugs that could be harmful to cats

A new test developed at Washington State University will help pharmaceutical companies, veterinarians and regulatory agencies identify drugs that may trigger severe - but preventable - neurological side effects in some cats.

Even in healthy cats, many commonly prescribed drugs can cause dangerous reactions when administered in specific combinations or when given to felines born with a mutation in their MDR1 gene. This mutation disrupts a protein called P-glycoprotein, which normally helps remove harmful substances from the brain and body, putting affected cats at risk for serious reactions from drugs that are perfectly safe for most cats.

Developed by WSU veterinary pharmacologist Dr. Katrina Mealey and laboratory supervisor Neal Burke, the test can determine if a drug relies on P-glycoprotein to be safely processed. Using the test, Mealey and Burke identified 10 new drugs that pose a risk to affected cats. The findings were detailed in the journal Frontiers in Veterinary Science. The method is available as a fee-for-service through WSU, or companies and governing agencies can use the published procedure to run their own screenings.

"This test allows us to screen both existing medications and new drug candidates, giving veterinarians, drug makers and regulators the information they need to make safer prescribing decisions," Mealey said. "By identifying drugs that could be dangerous for cats with the MDR1 mutation, it helps protect these cats and can prevent serious adverse reactions in the wider feline population. We hope it will eventually lead to warning labels, so veterinarians and pet owners have the guidance they need to keep cats safe. Human medications carry this information on the label so it seems reasonable that veterinary medications should too."

The feline MDR1 mutation, discovered by Mealey in 2015, is estimated to be present in up to 6% of Maine coon cats and roughly 1% of non-pedigreed cats in the United States and Europe. In 2001, Mealey also identified a similar MDR1 mutation in dogs. After each discovery, she developed the first tests, which can be administered by pet owners or veterinarians, to identify pets with the mutation, saving countless animal lives.

Even cats without the mutation can develop acquired P-glycoprotein deficiency, which can occur when drugs that are processed by P-glycoprotein are given together, since the medications can compete for clearance.

"It's not only cats with the mutation you have to worry about," Mealey said. "If some of these drugs are given in combination to any animal, you can see side effects because of drug interactions. This new test will help us to identify those drugs that could cause these reactions when given together."

Since the initial discoveries of the MDR1 mutations, Mealey has been working to identify drugs that cause harmful reactions in affected animals. She has already identified a long list of drugs, including parasiticides, anticancer drugs, gastrointestinal drugs, immunosuppressants and sedatives. Due to species differences, drugs toxic to dogs with the mutation may not have the same effects in cats.

The new test will make it easier to flag existing drugs that pose a risk and to spot potentially dangerous compounds being developed and before they reach the market. The test works by adding a fluorescent compound - normally cleared from cells by P-glycoprotein - along with a test drug to a feline cell culture. If the drug also depends on P-glycoprotein, the compound builds up and glows inside the cells, signaling a potential risk for cats with the MDR1 gene mutation.

The research was supported in part by the Everycat Feline Foundation, the Palouse Club and WSU donor Kay Fowler.

Media Contacts

• Katrina Mealey, WSU College of Veterinary Medicine, 509-335-2988, [email protected]
• Devin Rokyta, WSU College of Veterinary Medicine communications, 509-335-1911, [email protected]