Editorial: Can COVID-19 have a Clinically Significant Effect on Drug Metabolism? 2023 Ceban et al

Hepatic metabolism is one of three major routes of drug elimination. Drug metabolism generally involves a sequence of two reactions which allow for efficient excretion by the kidneys. Phase I reactions are catabolic and typically involve reduction, oxidation, or hydrolysis to convert lipophilic agents into more polar and reactive products. Phase II reactions are anabolic and consist of conjugation reactions with endogenous hydrophilic substances to further polarize and usually inactivate the parent drug [1]. The Cytochrome P450 (CYP450) enzymes, a set of heme proteins, frequently catalyze reactions involved in phase I metabolism. Although there exist 57 CYP isoforms in humans, not all are involved in drug metabolism, and CYP3A4/5, CYP2D6, CYP2C8/9, and CYP1A2 are responsible for the majority of reactions catalyzed by CYP450 [2]. Herein, we aim to explore the possibility of whether COVID-19 infection and associated inflammation can affect drug metabolism.

Open access, https://www.tandfonline.com/doi/full/10.1080/14740338.2023.2172158

 

"CONCLUSION & FUTURE DIRECTIONS

The consideration of whether individuals with post-COVID-19 condition exhibit a decreased capacity for drug biotransformation is topical given that hundreds of pharmacologic agents are currently being trialed, both formally (i.e., via clinical trials) [26] and informally (i.e., off label use) to treat aspects of the condition. For example, the metabolism of antidepressants such as selective serotonin uptake inhibitors (SSRIs) (e.g., fluvoxamine), and tricyclic antidepressants (TCAs), frequently prescribed for the management of neuropathic pain, cognitive deficits, and mood symptoms, may be particularly affected as many of these agents are substrates of CYP450. Parenthetically, fluvoxamine, which is currently being trialed for the treatment of long COVID [27], is a pan-CYP450 inhibitor in and of itself.

Furthermore, medications metabolized primarily by CYP3A4, as well as those with narrow therapeutic indices and/or safety concerns in situations of decreased functional activity (e.g., Valbenazine), and decreased CYP2D6 activity, may be particularly affected by post-COVID-19 condition. Taking into account that individuals with chronic inflammatory conditions (e.g., diabetes, cardiovascular disease, mood disorders) [28] are at a greater risk of experiencing a severe COVID-19 episode, and may be at an increased risk of developing post-COVID-19 condition, the efficacy and tolerability of medications used to manage the foregoing conditions should be closely monitored post-infection. Taken together, a clarion call is warranted for researchers to characterize the effect of COVID-19-induced inflammation on the pharmacokinetics of medications and its implications for their effectiveness and safety."