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The COVID-19 outbreak, which was prompted by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, continues to spread over the world. In the pathophysiology of COVID-19, the immunological response of the patient is crucial. The immunological changes occur when the immune system is fighting against SARS-CoV-2 and the signal becomes hyperactive. In drug metabolism and transport mechanism, a hyperimmune state can cause severe abnormalities. As a result, inter-individual variability in drug pharmacokinetics may occur, potentially leading to unexpected treatment responses. The physiology of drug transporters and drug-metabolizing enzymes are also affected in COVID-19 patients with autoimmune and metabolic disorders. The Food and Drug Administration (FDA) has approved several antiviral and anti-inflammatory drugs to treat COVID-19 patients based on the evidence, despite the fact without knowing any possible interactions with each other. Inflammation directs the altered expression of drug-metabolizing enzymes and drug transporters, shown by preclinical and clinical research. A deeper understanding of the impact of immune responses on drug metabolism and transport, as well as the therapeutic implications of this knowledge, would aid in the personalization of drug treatment. The current review summarizes the effect of inflammation and the complement system on the pharmacokinetics of COVID-19 medications by altering the expression and activity of drug transporters and drug-metabolizing enzymes, as well as offers an opinion on possible drug-drug interactions in disease states. More studies …