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It’s
only spit, but what’s inside your saliva may
help solve a dosing dilemma facing doctors and patients.
By using DNA to customize prescriptions, researchers
at Temple University’s School of Pharmacy are
working to prevent adverse drug reactions before you
even take the first dose. Each year, adverse drug reactions
kill or injure more than 770,000 people in this country,
according to the U.S. Department of Health & Human
Services. At the top of the list of problem drugs is
Warfarin, (Coumadin®), the most widely prescribed
anticoagulant. That is why Evgeny Krynetskiy, Ph.D.,
associate professor and director of the Jayne Haines
Center for Pharmacogenomics and Drug Safety, has focused
his research efforts on that drug.
“Prescribing this medicine is like trial and
error in finding the right dosage that works best for
you,” says Krynetskiy. “Five milligrams
is a typical dose, but a little less or a little more
could have dramatic consequences or no benefit at all.” |
Photo by Joseph V. Labolito/Temple
University
What students can learn from
saliva:
The medical community is learning how to use genetic information to tailor
drug regimens for patients, and so are students, by genotyping themselves. Here,
second-year Pharm.D. student Regies Cyriac is introduced to pharmacogenomics. All
153 students will extract their own DNA through collected saliva samples to see
how they would react to the anti-tuberculosis drug Isoniazid.
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Doctors call this optimal dosage
the therapeutic window, and Krynetskiy is trying
to find it through pharmacogenomics, the study of
a person’s
response to drugs based on their genetic makeup.
It’s a collaboration that crosses campuses
and includes Krynetskiy and fellow clinical faculty
at the School of Pharmacy, clinicians at Temple University
Hospital and Jeannes Hospital. The researchers are
studying why people process the same drug differently.
In this case, they’re trying to find the correlation
between genotypes, or a person’s inner code
of DNA, and the correct dosage of Warfarin. By collecting
saliva samples and extracting DNA from 77 participants
already on the drug, the researchers can look for
variances, genetic clues, which make people metabolize
the same drug in very different ways.
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Photo by Ryan S. Brandenberg/Temple University
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“Our
findings have confirmed there is a genetic variance
of certain genotypes that correlate to how these participants
respond to this drug,” says co-investigator Nima
Patel, Pharm. D., associate professor in the School
of Pharmacy. “So, if you have this genotype,
we can conclude what your risks may be, based on your
DNA.”
That would allow doctors to prescribe the correct dosage of Warfarin and decrease
the risk of adverse drug reactions: Too low a dose can increase the risk of dangerous
blood clots, while too large can cause life-threatening bleeding. What may be
equally noteworthy about Krynetskiy’s and Patel’s research is
that more than half the participants are either African American or Hispanic,
two groups underrepresented in clinical trials. So, finding their therapeutic
window, the place where they will safely get the maximum benefit of a drug, is
particularly important in this personalized medicine quest.
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