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COVID-19 Vaccines and the Virus: Impact on Drug Metabolism and Pharmacokinetics

Journal

DRUG METABOLISM AND DISPOSITION
Volume 51, Issue 1, Pages 130-141

Publisher

AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.122.000934

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This article reports on a symposium held by the American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition, which discussed the impact of viral infections and vaccines on drug metabolism and disposition. The symposium discussed the interactions between viral infections and hepatic drug metabolism, as well as the potential effects on drug absorption, distribution, metabolism, and excretion. The discussions also covered how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs and their potential impact on fetal development.
This article reports on an American Society of Pharmacology and Therapeutics, Division of Drug Metabolism and Disposition symposium held at Experimental Biology on April 2, 2022, in Philadelphia. As of July 2022, over 500 million people have been infected with SARS-CoV-2 (the virus causing COVID-19) and over 12 billion vaccine doses have been administered. Clinically significant interactions between viral infections and hepatic drug metabolism were first recognized over 40 years ago during a cluster of pediatric theophylline toxicity cases attributed to reduced hepatic drug metabolism amid an influenza B outbreak. Today, a substantive body of research supports that the activated innate immune response generally decreases hepatic cytochrome P450 activity. The interactions extend to drug transporters and other organs and have the potential to impact drug absorption, distribution, metabolism, and excretion (ADME). Based on this knowledge, altered ADME is predicted with SARS-CoV-2 infection or vaccination. The report begins with a clinical case exploring the possibility of SARS-CoV-2 vaccination increasing clozapine levels. This is followed by discussions of how SARS-CoV-2 infection or vaccines alter the metabolism and disposition of complex drugs, such as nanoparticles and biologics and small molecule therapies. The review concludes with a discus-sion of the effects of viral infections on placental amino acid trans-port and their potential to impact fetal development. The session improved our understanding of the impact of emerging viral infec-tions and vaccine technologies on drug metabolism and disposi-tion, which will help mitigate drug toxicity and improve drug and vaccine safety and effectiveness.

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