Drug Interactions

Unlike treatment for many other diseases, HIV therapy involves a cocktail of antiretroviral drugs. How those drugs interact with each other and with medication that patients might take for other conditions is a key issue in drug development.

“Usually drug interaction is manageable in the general population because people are taking one or two drugs,” Kashuba says. “In HIV, just for the HIV therapy, people are taking at least three, sometimes up to five or eight drugs.”

Kashuba studies drug interaction through phenotyping, a technique that she has been honing since her fellowship. A known drug is given to a volunteer, and researchers measure how quickly a particular enzyme breaks down that drug, which establishes a baseline for comparison. Then for seven to fourteen days, the volunteer is given a drug that is under development. After that time, the volunteer is given the known drug again to measure how long it takes the enzyme to break down the known drug in the presence of the new drug. This will provide an idea about the drug-interaction potential of the drug under development. 

The data gathered through phenotyping helps industry and the FDA decide which other drug-interaction studies to pursue. When the information is included in the drug’s package insert, it also helps physicians and pharmacists determine which concomitant medications can be given safely with the drug of interest.

Kashuba’s technique has caught the attention of the FDA. The agency issued a draft guidance document in September 2006 advising drug companies to use the method for testing drug interactions. The FDA used Kashuba’s research, among others, as the basis for the document.

“The drugs they recommend and the methods that they recommend are what I’ve been working on up to this point,” Kashuba says. “We have done a lot of work with industry, a lot of collaboration with industry, to use this technique to understand the drug-interaction potential for their drugs.

“We’re not the only ones who are working in this area, but we have got the techniques down very robustly and in a very sensitive manner. We’re one of the leaders in this particular area."

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