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Probenecid: Makes Tamiflu Last Longer

November 7, 2005

Probenecid, a drug used during World War II to augment the effects of antibiotics - and thus make better use of supplies - may prove useful in responding to an avian influenza pandemic. An American doctor, Dr Joseph Howton, from the Adventist Medical Centre, claims that combined use of probenecid with Tamiflu (oseltamivir) has the effect of making Tamiflu last twice as long, according to a report by ABC News online.

According to Dr Howton, he was reviewing studies on drug interactions when he discovered the idea of combining the drugs to gain a more extended effect.

"I found that they talk about being careful when you use probenecid with Tamiflu because it raises the drug level," he said, according to ABC News online. "I thought about it from the opposite perspective: this a wonderful side effect.

"If you look at Tamiflu the same way we looked at penicillin during World War II - and penicillin was in very short supply - and as a result we gave probenecid with penicillin to enhance the effect and extend the supplies.

"Why not use that same idea for Tamiflu?"

Probenecid reduces the amount of uric acid in the body by causing more uric acid to be passed out in the urine. It is primarily used to treat gout and gouty arthritis.

Dr Howton notes that, for some drugs, probenecid reduces the amount that is excreted from the body.

"Tamiflu is a drug that's a weak organic acid," he said. "Probenecid blocks organic acid from being excreted by the kidneys...and therefore you have much less of the intact drug excreted.

"It stays around and recirculates and you have better virus-killing effect."

Uses of Probenecid

Dr Howton notes that the augmenting properties of Probenecid may offer advantages in two ways.

"We can give a half-dose of, or even less than half of a dose of Tamiflu, along with Probenecid and we should get roughly the same levels as if we had just given a full dose," he said. "Therefore we can treat twice as many people with the same amount of drug.

"Another approach might be to use a standard dose of Tamiflu, along with Probenecid, and thereby getting a higher than usual tissue level of Tamiflu, which might actually be necessary."

However, he cautions that the discovery will not actually prevent a bird-flu pandemic.

"The only way we're going to prevent just massive numbers of fatalities in the event or a major pandemic is by a vaccine," he said. "The whole idea of a drug like Tamiflu is to buy us time, so that the vaccine can be developed."

Research on Probenecid was published in the 3 November 2005 issue of Nature.

Posted: November 2005