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From Genes to Medications: ADME and Pharmacogenomics in Personalized Care

15 October 2024

ADME PGx Blog Cover

The intricate interplay between drug ADME (Absorption, Distribution, Metabolism, and Excretion) and Pharmacogenomics (PGx) is a fascinating area of study within the field of personalized medicine. Understanding how these factors interact is essential for tailoring drug therapies to individual patients and optimizing treatment outcomes.

The Processes of Drug - ADME

ADME encompasses four key processes that dictate how drugs behave in the body:

https://toolbox.eupati.eu/glossary/pharmacokinetics/
Source: Eupati (The key principles of Pharmacokinetics – the study of the effect the body has on a medicine – are represented in the acronym ADME)

Absorption

This is about how drugs get into your body through the bloodstream. It depends on how the drug is given, what it’s made of, and how your body works. Some people can absorb drugs faster or better than others because of differences in the genes that handle drug transport and metabolism. ¹ ³

Distribution

Once a drug gets into your body, it has to reach the right place. This depends on things like how blood flows, what your tissues are like, and how drugs attach to proteins. Pharmacogenomics can help find genetic differences that affect how proteins work and how they move drugs around. This can affect how well a treatment works. ² ⁵

Metabolism

This is about how your body changes a drug into its active or inactive forms. Enzymes mainly control this process. Genetic differences in the genes that make these enzymes can really change how your body handles drugs. Some people process drugs very quickly, which might not be effective, while others process them slowly, which can lead to too much of the drug in the body and possible harm. ⁴ ⁶

Excretion

The last part of drug handling (ADME) is getting rid of the byproducts after a drug has done its job. Genetic differences can also affect how well your body gets rid of drugs and their leftovers. Some people can remove drugs from their bodies quickly, while others might take longer, which can keep the drug in their system for a while. ¹ ²

Pharmacogenomics and Personalized Medicine

Absorption

This process involves how drugs enter the bloodstream. Factors influencing absorption include the method of administration, the drug’s formulation, and individual physiological characteristics. Genetic variations can affect the efficiency of drug transporters, leading to differences in absorption rates among individuals.

Distribution

After absorption, drugs must reach their target sites. This distribution is influenced by blood flow, tissue characteristics, and protein binding. Pharmacogenomics can identify genetic differences that affect protein function and drug transport, impacting therapeutic efficacy.

Metabolism

This refers to how the body chemically alters drugs, primarily through enzymatic activity in the liver. Genetic polymorphisms in metabolic enzymes can lead to significant variability in how quickly or effectively a drug is processed. Some individuals may metabolize drugs too quickly, reducing effectiveness, while others may do so too slowly, risking toxicity.

Excretion

The final phase involves eliminating drug metabolites from the body, primarily through the kidneys or liver. Genetic factors can influence excretion rates, affecting how long a drug remains active in the system.

Pharmacogenomics, on the other hand, focuses on how an individual’s genetic makeup influences their response to drugs. This field seeks to identify specific genetic differences or variations, known as polymorphisms, that can impact drug efficacy, safety, and side effects. By understanding a patient’s genetic profile, healthcare providers can make more informed decisions about which drugs to prescribe, at what dosages, and how frequently to monitor the patient during treatment.

The integration of drug ADME and pharmacogenomics is particularly powerful for achieving personalized medicine. For example, by looking at a person’s genetic differences in how they process and transport drugs, doctors can choose medicines that are more likely to work well, be spread throughout the body correctly, be processed properly, and be removed efficiently. This minimizes the risk of adverse effects and improves the likelihood of treatment success.

In summary, the synergy between drug ADME and pharmacogenomics is a fundamental aspect of personalized medicine. By understanding how genetic variations influence drug processes and responses, healthcare providers can optimize treatment plans, enhance therapeutic outcomes, and reduce the potential for adverse reactions. This integrated approach holds immense potential for improving patient care and revolutionizing the field of medicine.

¹ American Society of Health-System Pharmacists. (2019). Pharmacogenomics: A guide for the pharmacy professional. https://www.ashp.org/-/media/assets/policy-guidelines/docs/pharmacogenomics-guide.pdf

² Johnson, J. A., & Cavallari, L. H. (2015). Pharmacogenetics and cardiovascular disease: The role of genetics in drug response. Circulation Research, 117(3), 247-257. https://doi.org/10.1161/CIRCRESAHA.117.303123

³ Wang, H., & Zhang, Y. (2020). Advances in pharmacogenomics: Implications for clinical practice. Journal of Personalized Medicine, 10(4), 1-12. https://doi.org/10.3390/jpm10040012

⁴ Ingelman-Sundberg, M. (2017). Pharmacogenomic biomarkers in drug development and clinical practice: A review of the current landscape and future perspectives. Nature Reviews Drug Discovery, 16(5), 355-370. https://doi.org/10.1038/nrd.2017.14

⁵ U.S. Food and Drug Administration. (2021). Table of pharmacogenomic biomarkers in drug labeling. https://www.fda.gov/media/144334/download

⁶ Relling, M. V., & Evans, W. E. (2015). Pharmacogenomics in the clinic. Nature, 526(7573), 343-350. https://doi.org/10.1038/nature15816