Ever wonder why a certain medication may work great for a friend and do nothing for you? Interestingly, it could involve specific genes that transport the medication into and out of your cells.
Fexofenadine (brand names are Allegra, Aller-ease) is a commonly used allergy medication. Say that you have watery eyes and a drippy nose during spring allergy season, and take some fexofenadine to help with the symptoms.
Once swallowed, that medication dissolves, gets absorbed, and then transported to the cells where it acts. Then, it needs to stay inside those target cells to have an effect.
How the medication stays inside the cells – instead of being transported right back out of the cell – is where genetics comes into play.
Certain medications and toxins are transported back out of cells by an ATP-binding cassette transporter protein encoded by the ABCB1 gene.
In the epithelial cells lining your intestines, the ABCB1 proteins are involved in the pumping of substances back into the intestinal lumen.
Imagine taking a fexofenadine pill: it then dissolves, gets absorbed, and then part of that gets pumped back into the intestines to be eliminated.
Genetic variants in ABCB1 affect how much of the substance stays in the cell compared to how much gets excreted back out of the cell.
In general, it is a good thing for the body to get rid of a substance that it thinks might be toxic. But when it comes to medications, this can create problems. While an allergy medication not working well for you isn’t really a big deal, the real problem comes when trying to keep chemotherapy drugs inside of cancer cells. Thus, this gene has been studied in depth for drugs that treat cancer.
If you carry one of the variants above, you may be wondering what you can do to increase the effectiveness of your allergy medicine during this pollen season.
Bedada, Satish Kumar, and Praveen Kumar Boga. “The Influence of Piperine on the Pharmacokinetics of Fexofenadine, a P-Glycoprotein Substrate, in Healthy Volunteers.” European Journal of Clinical Pharmacology, vol. 73, no. 3, Mar. 2017, pp. 343–49. PubMed, https://doi.org/10.1007/s00228-016-2173-3.
Bermúdez de León, Mario, et al. “Association Study of Genetic Polymorphisms in Proteins Involved in Oseltamivir Transport, Metabolism, and Interactions with Adverse Reactions in Mexican Patients with Acute Respiratory Diseases.” The Pharmacogenomics Journal, vol. 20, no. 4, Aug. 2020, pp. 613–20. PubMed, https://doi.org/10.1038/s41397-020-0151-8.
Hama, Rokuro. “The Mechanisms of Delayed Onset Type Adverse Reactions to Oseltamivir.” Infectious Diseases (London, England), vol. 48, no. 9, Sept. 2016, pp. 651–60. PubMed Central, https://doi.org/10.1080/23744235.2016.1189592.
Han, Nayoung, et al. “Assessment of Adverse Events Related to Anti-Influenza Neuraminidase Inhibitors Using the FDA Adverse Event Reporting System and Online Patient Reviews.” Scientific Reports, vol. 10, Feb. 2020, p. 3116. PubMed Central, https://doi.org/10.1038/s41598-020-60068-5.
Jin, Ming-Ji, and Hyo-Kyung Han. “Effect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food-Drug Interaction.” Journal of Food Science, vol. 75, no. 3, Apr. 2010, pp. H93-96. PubMed, https://doi.org/10.1111/j.1750-3841.2010.01542.x.
Laborda, Pedro, et al. “Influenza Neuraminidase Inhibitors: Synthetic Approaches, Derivatives and Biological Activity.” Molecules, vol. 21, no. 11, Nov. 2016, p. 1513. PubMed Central, https://doi.org/10.3390/molecules21111513.
Maxwell, Simon R. J. “Tamiflu and Neuropsychiatric Disturbance in Adolescents.” BMJ : British Medical Journal, vol. 334, no. 7606, June 2007, pp. 1232–33. PubMed Central, https://doi.org/10.1136/bmj.39240.497025.80.
Shi, Jian, et al. “Association of Oseltamivir Activation with Gender and Carboxylesterase 1 Genetic Polymorphisms.” Basic & Clinical Pharmacology & Toxicology, vol. 119, no. 6, Dec. 2016, pp. 555–61. PubMed, https://doi.org/10.1111/bcpt.12625.
Shon, Ji-Hong, et al. “Effect of Itraconazole on the Pharmacokinetics and Pharmacodynamics of Fexofenadine in Relation to the MDR1 Genetic Polymorphism.” Clinical Pharmacology and Therapeutics, vol. 78, no. 2, Aug. 2005, pp. 191–201. PubMed, https://doi.org/10.1016/j.clpt.2005.04.012.
———. “Effect of Itraconazole on the Pharmacokinetics and Pharmacodynamics of Fexofenadine in Relation to the MDR1 Genetic Polymorphism.” Clinical Pharmacology and Therapeutics, vol. 78, no. 2, Aug. 2005, pp. 191–201. PubMed, https://doi.org/10.1016/j.clpt.2005.04.012.
Singh, A. B., et al. “ABCB1 Polymorphism Predicts Escitalopram Dose Needed for Remission in Major Depression.” Translational Psychiatry, vol. 2, no. 11, Nov. 2012, pp. e198–e198. www.nature.com, https://doi.org/10.1038/tp.2012.115.
Tarkiainen, E. K., et al. “Carboxylesterase 1 Polymorphism Impairs Oseltamivir Bioactivation in Humans.” Clinical Pharmacology and Therapeutics, vol. 92, no. 1, July 2012, pp. 68–71. PubMed, https://doi.org/10.1038/clpt.2012.13.
Yi, So-Young, et al. “A Variant 2677A Allele of the MDR1 Gene Affects Fexofenadine Disposition.” Clinical Pharmacology and Therapeutics, vol. 76, no. 5, Nov. 2004, pp. 418–27. PubMed, https://doi.org/10.1016/j.clpt.2004.08.002.
———. “A Variant 2677A Allele of the MDR1 Gene Affects Fexofenadine Disposition.” Clinical Pharmacology and Therapeutics, vol. 76, no. 5, Nov. 2004, pp. 418–27. PubMed, https://doi.org/10.1016/j.clpt.2004.08.002.
