Every person responds to medication a little differently. For many, a standard dose is effective. For others, it may be ineffective and lead to uncomfortable or potentially dangerous reactions. One major reason for this variation lies in how each person’s body metabolizes, or processes, a drug.
At the University of Colorado Anschutz (CU Anschutz), researchers are studying how genetic differences shape these metabolic patterns. Their goal is to turn complex biology into practical tools that help clinicians choose safer, more precise treatments from the start.
Jack Staples, PhD, a postdoctoral fellow in the Claw Indigenous Genomics and Ethics Lab at the CU Anschutz Department of Biomedical Informatics (DBMI), explained pharmacogenetics through an analogy most people can visualize:
“In chemical process engineering, you never assume two bioreactors behave identically and the body is no different,” Staples said. “Genetics helps us understand each person's unique settings, so we can adjust treatment in safer, more reliable ways.”
In this “processing plant,” medications act as raw materials. As they move through the body, specialized “machines” (our organs) process, distribute and clear them. Pharmacogenetics studies how genetic differences influence the performance of those machines, shaping how individuals respond to the same drug.
Led by Katrina Claw, PhD, the Claw Lab is advancing research at the intersection of genomics and Indigenous health. Explore their work in our feature, Inside the Claw Lab: Where Genetics Meets Community.
Once a medication enters the body, it moves through a coordinated series of biological “stations,” each influencing how much of the drug is absorbed, how long it stays active, and how the body ultimately clears it. Understanding these steps helps explain why individuals can respond so differently to the same prescription.
Before a medication ever reaches the liver, it must pass through the gastrointestinal (GI) tract, the body’s first major processing gate. Here, several factors determine how much of a drug makes it into the bloodstream.
This “pre-processing” dramatically affects a drug’s bioavailability, the portion of the medication that becomes active in the body. For some individuals, gut microbes may speed up breakdown; for others, they may alter a drug in unexpected ways. This is why two people who take the same pill may absorb very different amounts.
The liver plays the starring role in drug metabolism, acting as the body’s primary processing hub. It contains specialized enzymes that transform medications into metabolites the body can use or eliminate.
But people don’t all have the same enzyme activity.
These differences can influence whether a medication provides relief, causes side effects, or misses its therapeutic window. By measuring metabolites in blood or urine, researchers can get a real-time readout of how efficiently someone’s “liver machinery” is operating.
After the liver finishes processing a drug, the kidneys take over. Their job is to filter the bloodstream and remove water-soluble metabolites so they can be excreted in the urine.
Kidney efficiency varies from person to person and can change with age, hydration, genetics, or medical conditions like hypertension and diabetes. When kidneys work efficiently, they clear metabolites at the expected rate. When they work more slowly, drug byproducts can build up, sometimes leading to toxic levels.
For certain medications, like antibiotics, pain relievers, or drugs for heart conditions, understanding kidney filtration rates is essential for safe dosing. This is why many prescriptions include recommended adjustments for people with reduced kidney function.
Once a drug enters the bloodstream, the heart and circulatory system act as the distribution network, delivering medication to organs, tissues, and cells.
Circulation doesn’t transform the drug, but it determines how efficiently the drug reaches its target. Variations in blood flow, heart function, and blood vessel health can shape how quickly or effectively medications spread throughout the body. In people with poor circulation or cardiovascular conditions, a standard dose may be slower to take effect or may concentrate differently in certain tissues.
These subtle differences in distribution help explain why a medication may feel powerful in one person and mild in another, even at the same dose.
A major piece of the puzzle is our DNA. Small genetic differences can affect the speed or strength of the enzymes and transporters that move drugs through the body.
“Your DNA is like the operating manual for key enzymes and transport systems that control drug metabolism and clearance,” said Staples. “Small genetic differences can change how fast those pathways run, almost like turning the dial up or down on reaction speed.”
By sequencing DNA and studying how individuals metabolize medications, researchers can build clearer, more quantitative predictions about how someone might response, not just labels like “fast metabolizer,” but more personalized expectations across a spectrum.
In the Claw Lab, researchers are using machine learning models to combine genetic information with metabolism data. These models help identify signals that indicate whether a typical dose might be too high, too low, or require closer monitoring.
This work is especially focused on ensuring that precision medicine benefits communities historically left out of genetic research.
“A major goal is to translate complex genetics and metabolism signals into something clinicians can actually use by discovering actionable indications that a typical dose may overshoot, fall short, or require closer monitoring of the therapeutic window required for efficacy,” said Staples. “We want these tools to work for everyone, not just people of European ancestry, who are often overrepresented in genetic studies.”
One project examines pathways involved in nicotine metabolism, but the same approach can be used for many other medications. The aim is to turn complex data into clear, indicators that clinicians can use to personalize care.
As these models continue to evolve, the Claw Lab hope they will make it easier for healthcare providers to:
By bringing together genetics, metabolism, and advanced analytics, the Claw Lab is helping build a future where medication decisions are more precise and more equitable, ensuring people from all communities can benefit from the promise of personalized medicine.