Tuberculosis Drug Dosing Gets a Closer Look
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Ambrose says that similar types of studies have been done for other drugs, but not for those used to treat TB, probably because they are so old. No new treatments have emerged for TB since the 1970s, though some new compounds are now being tested.
In the past, this type of individualized drug monitoring for TB has been done “only in patients who were failing therapy, and it has been largely limited to resource-rich settings like the U.S. and Europe,” says Eric Nuermberger, a physician at Johns Hopkins. Nuermberger is not involved in the study.
While pharmacogenomics—targeting drug dosages and selections of drugs to an individual’s genetic makeup—is only part of Gumbo’s strategy, experts say it will likely prove to be an important aspect of TB treatment. “We know that for isoniazid [a common TB drug], the global population as a whole splits into three different phenotypes; those who metabolize the drug quickly, those who metabolize it slowly, and intermediate metabolizers,” says Nuermberger. A dose that is appropriate for a slow metabolizer might be too low for a fast metabolizer; likewise, a higher dose appropriate for a fast metabolizer might increase side effects for a slow metabolizer.
“The other cornerstone first-line drug for TB, rifampicin, has been notorious for having highly variable drug exposures,” adds Nuermberger. “If you look at 100 people who take it, you’ll see a tenfold difference in exposure,” the concentration and length of time that drug is in a person’s bloodstream before being metabolized, he says. “We are now starting to understand there are genetic differences that determine drug exposure. And there is hope that we can develop genetic tests to use in the field.”
While it may be difficult to imagine implementing genetic testing in a poor country with an already strained medical system, Nuermberger doesn’t rule it out. “We will continually develop cheaper and easier tests that could be implemented at the point of care,” he says. “We thought it would be difficult to implement drug-resistance tests, but those are now being used in reference labs, and a new device is moving even closer to the point of care.”
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