For this study, the researchers gave patients Pyrazinamide an older drug generally used in combination with other drugs daily for one month. The researchers then used the data collected to calculate how much bacteria the drug killed before resistance emerged. They opted to focus on Pyrazinamide because physicians once used it alone to treat the disease, so there are many studies documenting precisely how the drug behaves in patients something that is unclear for some newer drugs.
When the UT Southwestern researchers began testing Pyrazinamide in the lab, they found that the concentration of the drug declined at a rate that matches the rate seen in patients.
"In patients, unlike in test tubes, it's not a constant concentration. A patient given multiple drugs degrades each of them at different rates," he said. "Using this model, we can actually copy this concentration profile of the drugs to human-like exposures."
Dr. Gumbo said his team's finding that the doses traditionally given to tuberculosis patients are much too low suggests that different doses are probably needed in different countries. "Most of the patients we see here in Dallas are not 110 pounds unless they have some other severe disease," he added.
The next step, Dr. Gumbo said, is to continue researching drug combinations in order to devise the optimum treatment regimen for tuberculosis patients.
"We've rationally and scientifically come up with a dose that depends not just on the kinetics or the concentration time profile of patients, but also how the bug itself responds to that particular drug," he said. "So, instead of using the average patient or a mean patient, we can now project how a drug combination will fare in actual patients.
|Contact: Kristen Holland Shear|
UT Southwestern Medical Center