Fosamprenavir 700mg tablets

Background: A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: Darunavir (Daru), Dexamethasona (Dexame), Dolutegravir (Dolu), Fosamprenavir (Fosam), Ganciclovir (Gan), Insoine (Inso), Lopinavir (Lop), Ritonavir (Rito) and Tipranavir (Tipra). Methods: These ligands were analyzed using molecular docking, molecular quantum similarity using four similarity indices like overlap, Coulomb and their Euclidean distances. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LYS621, ARG555 and ASP623, CYS622, ASP760, among others. In the molecular quantum similarity, the highest indices have been obtained in the electronic similarity in comparison with the structural similarity. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

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Abstract Background Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia and can promote laryngeal carcinogenesis. More than 20% of the US population suffers from LPR and there is no effective medical therapy. Pepsin is a predominant source of damage during LPR which disrupts laryngeal barrier function potentially via E‐cadherin cleavage proteolysis and downstream matrix metalloproteinase (MMP) dysregulation. Fosamprenavir (FDA‐approved HIV therapeutic and prodrug of amprenavir) is a pepsin‐inhibiting LPR therapeutic candidate shown to rescue damage in an LPR mouse model. This study aimed to examine amprenavir protection against laryngeal monolayer disruption and related E‐cadherin proteolysis and MMP dysregulation in vitro. Methods Laryngeal (TVC HPV) cells were exposed to buffered saline, pH 7.4 or pH 4 ± 1 mg/mL pepsin ± amprenavir (10–60 min). Analysis was performed by microscopy, Western blot, and real time polymerase chain reaction (qPCR). Results Amprenavir (1 μM) rescued pepsin acid‐mediated cell dissociation ( p < .05). Pepsin acid caused E‐cadherin cleavage indicative of regulated intramembrane proteolysis (RIP) and increased MMP‐1,3,7,9,14 24‐h postexposure ( p < .05). Acid alone did not cause cell dissociation or E‐cadherin cleavage. Amprenavir (10 μM) protected against E‐cadherin cleavage and MMP‐1,9,14 induction ( p < .05). Conclusions Amprenavir, at serum concentrations achievable provided the manufacturer's recommended dose of fosamprenavir for HIV, protects against pepsin‐mediated cell dissociation, E‐cadherin cleavage, and MMP dysregulation thought to contribute to barrier dysfunction and related symptoms during LPR. Fosamprenavir to amprenavir conversion by laryngeal epithelia, serum and saliva, and relative drug efficacies in an LPR mouse model are under investigation to inform development of inhaled formulations for LPR.

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Objectives: Approximately 25% of Americans suffer from laryngopharyngeal reflux (LPR), a disease for which no effective medical therapy exists. Pepsin is a predominant source of damage during LPR and a key therapeutic target. Fosamprenavir (FOS) inhibits pepsin and prevents damage in an LPR mouse model. Inhaled FOS protects at a lower dose than oral; however, the safety of inhaled FOS is unknown and there are no inhalers for laryngopharyngeal delivery. A pre-Good Lab Practice (GLP) study of inhaled FOS was performed to assess safety and computational fluid dynamics (CFD) modeling used to predict the optimal particle size for a laryngopharyngeal dry powder inhaler (DPI). Methods: = 6) in an LPR mouse model. Organs (nasal cavity, larynx, esophagus, trachea, lung, liver, heart, and kidney) were assessed by a pathologist and bronchoalveolar lavage cytokines and plasma cardiotoxicity markers were assessed by Luminex assay. CFD simulations were conducted in a model of a healthy 49-year-old female. Results: No significant increase was observed in histologic lesions, cytokines, or cardiotoxicity markers in FOS or APR groups relative to the control. CFD predicted that laryngopharyngeal deposition was maximized with aerodynamic diameters of 8.1-11.5 μm for inhalation rates of 30-60 L/min. Conclusions: A 4-week pre-GLP study supports the safety of inhaled FOS. A formal GLP assessment is underway to support a phase I clinical trial of an FOS DPI for LPR. Level of Evidence: NA.

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• Creation of the first MIP-based sensor for electrochemical determination of fosamprenavir . • Comparison of the validation parameters for two distinct MIP approaches. • The effective utilization of sensors for fosamprenavir measurement in actual samples. • Assessment of the sensor's accuracy via a thorough computational study. Fosamprenavir (FPV) is combined with other drugs to manage human immunodeficiency virus infection patients. This prodrug was created to address the solubility issue of the parent protease inhibitor medication, amprenavir. Based on photopolymerization (PP) with p -aminophenol (PAP) functional monomer and electropolymerization (EP) with p -aminobenzoic acid (PABA) functional monomer, this work reported the effective invention of two distinct imprinting techniques for the specific and precise detection of FPV. The proposed sensors were characterized through the application of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and various electrochemical techniques. For both approaches, the necessary optimization research was carried out. The analytical characteristics of PP-FPV@MIP/GCE and EP-FPV@MIP/GCE sensors were assessed. The sensors' performance parameters were validated and compared, after constructing the most optimal MIP-integrated electrochemical sensors. In both standard preparations and commercial human serum preparations, for PP-FPV@MIP/GCE and EP-FPV@MIP/GCE, the linear ranges are 1.0–17.5pM and 1.0–10.0pM, respectively. In standard preparations, the limits of detection (LOD) for PP-FPV@MIP/GCE and EP-FPV@MIP/GCE were 2.84 × 10 −13 M and 2.27 × 10 −13 M, respectively, whereas in serum preparations, they were 2.48 × 10 −13 M and 2.38 × 10 −13 M. The developed electrochemical sensors show excellent recovery values when used to evaluate FPV in tablet preparations and commercial blood samples. The selective capability of the sensors towards FPV was investigated in the presence of comparable antiviral drugs. The impacts of ions, possible biological substances, and storage stability were investigated for the developed sensors. Density functional theory (DFT) calculations were employed to analyze the interaction energies between the template and functional monomers, providing insights into the interactions. These calculations complemented the experimental optimization of the template:monomer ratio by helping to understand the overall trends in molecular interactions.

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Fosamprenavir is a prodrug designed to overcome the solubility challenge of the parent drug amprenavir, a protease inhibitor. For the marketed oral suspension (Telzir®) a clinically documented negative food effect has been reported. The present study aims to gain a better mechanistic understanding of the food effect by in vitro tests on solubility, bioconversion, permeability, and dynamic dissolution/bioconversion/permeation studies in a high throughput manner on a microtiter plate (Permeapad® Plate). In order to mimick luminal condition changes in connection with food, various modified versions of fasted and fed state simulated intestinal fluids (FaSSIF-V2) and (FeSSIF–V2) were used. The kinetics of enzymatic cleavage (simulated bioconversion) were studied in these media with a focus on molecularly dissolved drug concentrations using microdialysis. Dynamic dissolution/bioconversion/permeation experiments, indicated the following factors to contribute to reduced permeation in fed state: elevated inorganic phosphate concentrations, higher concentrations of bile salts and lipids and lower intestinal pH. The impact of these effects is difficult to capture in vivo due to their interconnection and large variability between individuals. This study revealed factors leading to an altered luminal behavior of Telzir® oral suspension in fed state, which may contribute to explain the observed reduced amprenavir absorption from the suspension. Especially the high throughput small-scale dissolution/bioconversion/permeation experiments on a microtiter plate were demonstrated an efficient and powerful tool for elucidating the food effects of phosphate-ester prodrug type drug products as far as their altered luminal behavior is concerned.

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The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems.

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In the pharmaceutical industry, deep eutectic solvents can be used to enhance the solubility, permeability, and absorption of active pharmaceutical ingredients. In this paper, deep eutectic solvents were prepared by combining the active pharmaceutical ingredient fosamprenavir calcium with lactic acid in certain molar ratios. The aim of this study was to create a therapeutic deep eutectic solvent with the same therapeutic effect as the active pharmaceutical ingredient, but with enhanced properties. 1H NMR and FTIR spectroscopy were used to identify and characterize the chemical composition and structural changes of the prepared THEDES. Maximum solubility, the release of the active pharmaceutical ingredient from the therapeutic deep eutectic solvent, and permeability were tested. Different mathematical models were chosen to describe the kinetic behavior of the drug release.

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