Abstract
Hepatic cytochrome P450 3A4 (CYP3A4) is an important drug-metabolizing enzyme as it is responsible for metabolizing over 30% of currently marketed drugs across most therapeutic classes. CYP3A4 is regulated at various stages including transcriptional, post-transcriptional, translational and post-translational expression. Changes made at any of these stages of CYP3A4 regulation could result in fluctuations in CYP3A4 levels and/or activity. These alterations are important to understand as they could lead to drug–drug interactions, sub-therapeutic levels or toxic levels of pharmaceutical drugs. Nanomedicine, the use of nanotechnology for treatment, diagnosis and monitoring of biological systems, is a growing market. This includes use of viral vectors for gene transfer and vaccine applications and nanoparticles based on gold and silver for various applications. Both have shown to alter CYP3A4 activity and function. Hence, during pre-clinical and clinical studies it is important to elucidate any effect of nanomedicines on CYP3A4 to avoid unintended changes in maintenance of medications due to changes in drug metabolism.
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These authors (Kristina Jonsson-Schmunk, Stephen C. Schafer, and Maria A. Croyle) declare that they have no conflict of interest.
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This article does not contain any studies with human and animal subjects performed by any of the authors. All the studies are performed in accordance with the ethical standards by the principles of the Declaration of Helsinki.
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This work is supported by the National Institutes of Health NIGMS Grant R21GM69870, NIAID Grant U01AI078045 (MAC), and a Special Research Grant from the VP of Research at the University of Texas at Austin (MAC). This research was also supported by a University of Texas at Austin Continuing Graduate School Fellowship (KJS).
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Jonsson-Schmunk, K., Schafer, S.C. & Croyle, M.A. Impact of nanomedicine on hepatic cytochrome P450 3A4 activity: things to consider during pre-clinical and clinical studies. Journal of Pharmaceutical Investigation 48, 113–134 (2018). https://doi.org/10.1007/s40005-017-0376-y
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DOI: https://doi.org/10.1007/s40005-017-0376-y