Background: The US FDA has approved paxlovid, a combination of nirmatrelvir and ritonavir, as the first oral treatment for the management of mild-to-moderate COVID-19 patients.
Objective: The purpose of this review article is to explore the clinical data that is currently available regarding the drug-drug interactions (DDIs) of paxlovid with various medications.
Methods: Keywords, such as drug interactions, paxlovid, ritonavir, nirmatrelvir, pharmacokinetic interactions, CYP3A, and P-glycoprotein, were used to search online databases, including LitCOVID, Scopus, Embase, EBSCO host, Google Scholar, ScienceDirect, Cochrane Library, and reference lists.
Results: Paxlovid interacted with a variety of medications due to strong inhibition of CYP3A4 and P-gp transporter protein by ritonavir and the dual function of nirmatrelvir as a substrate and inhibitor of CYP3A enzymes and P-gp transporter protein. Numerous case reports and other studies determined that the risk of toxicities of several drugs, including anticoagulants (warfarin, rivaroxaban), calcium channel blockers (nifedipine, manidipine, verapamil), statins (atorvastatin), immunosuppressants (tacrolimus), antiarrhythmics (amiodarone), antipsychotics (clozapine, quetiapine), and ranolazine have been enhanced by the concomitant administration of paxlovid.
Conclusion: Adverse effects of paxlovid from DDIs can range from less-than-ideal therapeutic responses to potentially fatal toxicities. Effective management requires close observation, adjustments to dosage, and assessment of substitute treatments. Collaboration between pharmacists and other medical professionals is necessary to guarantee effective and safe treatment outcomes of paxlovid therapy.
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http://dx.doi.org/10.2174/0113892002320326250123082112 | DOI Listing |
J Biomol Struct Dyn
March 2025
Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, Brazil.
ATP-binding cassette (ABC) proteins are membrane transporters responsible for metabolites and active substances removal from cells. Their genes' variations have been associated with protein function and expression defects. Familial Hypercholesterolemia (FH) patients hosting those alterations might compromise the efficacy of high-dose statin treatment, a primary therapeutic strategy.
View Article and Find Full Text PDFLab Chip
March 2025
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Current drug development pipelines are time-consuming and prone to a significant percentage of failure, partially due to the limited availability of advanced human preclinical models able to better replicate the complexity of our body. To contribute to an advancement in this field, we developed an multi-organ-on-a-chip system, that we named PEGASO platform, which enables the dynamic culturing of human cell-based models relevant for drug testing. The PEGASO platform is composed of five independent connected units, which are based on a previously developed millifluidic organ-on-a-chip device (MINERVA 2.
View Article and Find Full Text PDFFront Pharmacol
February 2025
Department of Pharmacy, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Background: Sirolimus is primarily metabolized by CYP3A4 and transported by P-gp. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted sirolimus concentrations.
Case Summary: In this case report, we investigate a pharmacokinetic drug-drug interaction between regorafenib and sirolimus, mediated by CYP3A4 and P-gp, in a 56-year-old Chinese male with recurrent hepatocellular carcinoma post-liver transplantation.
J Mol Graph Model
February 2025
Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt; Department of Engineering, College of Engineering and Technology, University of Technology and Applied Sciences, Nizwa 611, Oman; School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa. Electronic address:
P-glycoprotein (P-gp) transporter is included in the failure of various carcinoma chemotherapeutics because of the multidrug resistance (MDR) phenomenon, in which the chemotherapeutic drugs are eliminated from target cells. Consequently, inhibiting P-gp transporter function is a prospective strategy for cancer treatment. In the current study, the SuperDRUG2 database containing >4600 pharmaceutical compounds was virtually screened toward the P-gp transporter utilizing the docking predictions.
View Article and Find Full Text PDFNucleosides Nucleotides Nucleic Acids
March 2025
Biology Department, Lebanese University, Beirut, Lebanon.
Lipids and glucose are important components of energy metabolism closely linked to each other. Glucose regulates cholesterol uptake regulating the expression of different membrane transport proteins including NPC1L1, SR-B1 and ATP-binding cassette (ABC) transporters. Here, we explored further the mechanism underlying glucose-mediated regulation of cholesterol absorption and secretion.
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