Researchers probe strategy to make flu drugs go further

August 3, 2009

On the line—Production at VA's Clinical Research Pharmacy Coordinating Center.(Photo by Bill Armstrong).

During this year's outbreak of swine flu, or H1N1, the treatment of choice—outside of vaccination—has been oseltamivir, sold as Tamiflu. The oral drug blocks an enzyme that allows the virus to reproduce and spread.

Stockpiles of the drug are considered adequate as of now. But the outbreak was upgraded to pandemic status back in June, and the virus continues to spread worldwide. Will there be enough oseltamivir to go around?

VA researchers have been studying one way to make the drug go further: Combine it with another drug that keeps it in the bloodstream longer.

A trial led by Mark Holodniy, MD, an infectious disease specialist at the VA Palo Alto Health Care System, showed that such an approach could be safe and feasible. Volunteers who took probenecid capsules four times daily, along with oseltamivir, over two weeks were able to take the flu drug every other day, instead of daily, and still keep enough in their bloodstream.

Probenecid has been used in a similar way for decades to extend the effects of penicillin and other antibiotics, so safety concerns with the drug are minimal. But one potential hitch with the regimen tried in the VA clinical trial is that getting people to take a drug four times a day can be an uphill battle. "It doesn't seem sustainable," says Holodniy. "We know that adherence to drug regimens in HIV and other diseases is a critical point. Are people able to sustain this for two weeks? We don't know. Some people have trouble just taking a vitamin once a day."

Enter VA's Clinical Research Pharmacy Coordinating Center. The Albuquerque facility serves as a pharmacy for large VA clinical trials. Now, with partners at the University of New Mexico, research pharmacists at the site are developing a sustained-release version of probenecid. The idea is for patients to be able to take that drug only once daily.

"We've done some proof-of-concept piloting in test tubes and shown that we can get a fair amount of probenecid in a pill that can be designed for sustained release, such that we might be able to back it down to twice a day or even once a day," says Holodniy. "This has not been previously developed or marketed, so it would be a new concept. This could allow people to be more adherent and make it a more viable regimen."

Holodniy points out that the strategy is far from being ready for prime time. The oseltamivir-probenecid combination would still have to undergo further clinical trials and receive approval from the Food and Drug Administration. But if it proves viable, says Holodniy, it could be of value in future flu pandemics.

This article originally appeared in the August 2009 issue of VA Research Currents.