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Allergologie Select 2023Not available.
Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for...
Not available.
PubMed: 37705676
DOI: 10.5414/ALX02422E -
Therapeutic Delivery Mar 2024Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Activation of prodrug was studied spectrophotometrically,...
Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.
PubMed: 38497152
DOI: 10.4155/tde-2023-0106 -
CPT: Pharmacometrics & Systems... Jan 2024Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the...
Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate-glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug-drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically-based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration-time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7-fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non-wild-type variants for both isoforms. This study is a first cornerstone to qualify the PK-Sim platform for use of UGT-mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.
Topics: Humans; Atazanavir Sulfate; Mefenamic Acid; Glucuronosyltransferase; Drug Interactions; Heterocyclic Compounds, 2-Ring; Pyrimidines
PubMed: 37794724
DOI: 10.1002/psp4.13059 -
Journal of Cancer Research and Clinical... Dec 2023This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. I was utilized as a radiolabeling isotope...
BACKGROUND
This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. I was utilized as a radiolabeling isotope to study the radio-kinetics of MEF niosomes.
METHODS
niosomal formulations were prepared by the ether injection method and assessed for entrapment efficiency (EE%), zeta potential (ZP), polydispersity index (PDI) and particle size (PS). MEF was labeled with I by direct electrophilic substitution reaction through optimization of radiolabeling-related parameters. In the radio-kinetic study, the optimal I-MEF niosomal formula was administered intravenously (I.V.) to solid tumor-bearing mice and compared to I.V. I-MEF solution as a control.
RESULTS
the average PS and ZP values of the optimal formulation were 247.23 ± 2.32 nm and - 28.3 ± 1.21, respectively. The highest I-MEF labeling yield was 98.7 ± 0.8%. The biodistribution study revealed that the highest tumor uptake of I-MEF niosomal formula and I-MEF solution at 60 min post-injection were 2.73 and 1.94% ID/g, respectively.
CONCLUSION
MEF-loaded niosomes could be a hopeful candidate in cancer treatment due to their potent tumor uptake. Such high targeting was attributed to passive targeting of the nanosized niosomes and confirmed by radiokinetic evaluation.
Topics: Mice; Animals; Liposomes; Mefenamic Acid; Tissue Distribution; Neoplasms
PubMed: 37982828
DOI: 10.1007/s00432-023-05482-8 -
AAPS PharmSciTech Jan 2024Alzheimer's disease (AD) is a very common disorder that affects the elderly. There are relatively few medications that can be used orally or as a suspension to treat AD....
Mefenamic Acid Loaded and TPGS Stabilized Mucoadhesive Nanoemulsion for the Treatment of Alzheimer's Disease: Development, Optimization, and Brain-Targeted Delivery via Olfactory Pathway.
Alzheimer's disease (AD) is a very common disorder that affects the elderly. There are relatively few medications that can be used orally or as a suspension to treat AD. A mucoadhesive (o/w) nano emulsion of mefenamic acid was made by adding Carbopol 940P to the optimised drug nanoemulsion using distilled water as the aqueous phase (6%); Solutol HS: tween 20 (3.6%) as the surfactant and co-surfactant; and clove oil: TPGS (0.4%) as the oil phase and mefenamic acid as the drug (2.8 mg/ml). The mucoadhesive nanoemulsion (S4) had a particle size of 91.20 nm, polydispersity index of 0.270, and surface charge of - 12.4 mV. Significantly higher (p < 0.001) drug release (89.37%) was observed for mucoadhesive drug formulation in comparison to mucoadhesive drug suspension (25.64%) at 8 h. The ex vivo nasal permeation of 83.03% in simulated nasal fluid and 85.71% in artificial cerebrospinal fluid was observed. The percent inhibition and inhibitory concentration (IC) of mucoadhesive drug nanoemulsion were found to be 91.57 ± 2.69 and 6.76 respectively. Higher cell viability on glioblastoma cells (85-80%) was researched for mucoadhesive nanoemulsion as compared to drug suspension (80-70%). Significantly higher (p < 0.001) drug absorption and Cmax (491.94 ± 24.13 ng/ml) of mucoadhesive drug nanoemulsion were observed than mucoadhesive drug suspension (107.46 ± 11.46 ng/ml) at 8 h. The stability studies confirmed that the formulation was stable at 40°C ± 2°C and 75 ± 5% RH. The authors concluded that the mucoadhesive mefenamic acid-loaded nanoemulsion may be an effective technique for treating Alzheimer's disease by intranasal route.
Topics: Humans; Aged; Mefenamic Acid; Olfactory Pathways; Alzheimer Disease; Brain; Surface-Active Agents; Vitamin E
PubMed: 38200387
DOI: 10.1208/s12249-023-02727-0 -
Spectrochimica Acta. Part A, Molecular... Nov 2023Abnormal levels of mefenamic acid (MFA) in living organisms can result in hepatic necrosis, liver, and gastrointestinal diseases. Therefore, development of accurate and...
Abnormal levels of mefenamic acid (MFA) in living organisms can result in hepatic necrosis, liver, and gastrointestinal diseases. Therefore, development of accurate and effective method for detection of MFA is of great significance for the protection of public health. Herein, we designed a stilbene based sensor ECO for the sensitive and selective detection of mefenamic acid by employing fluorescence spectroscopy for the first time. The developed sensor ECO displayed fluorescence turn-off response towards MFA based on PET (photoinduced electron transfer) and hydrogen bonding. The sensing mechanism of MFA was investigated through H NMR titration experiment and density functional theory (DFT) calculations. The presence of non-covalent interaction was confirmed through spectroscopic analysis and was further supported by non-covalent interaction (NCI) analysis and Bader's quantum theory of atoms in molecules (QTAIM) analysis. Additionally, the sensor ECO coated test strips were fabricated for on-site detection of mefenamic acid. Furthermore, the practical applicability of sensor ECO to detect MFA was also explored in human blood and artificial urine samples.
Topics: Humans; Mefenamic Acid; Fluorescent Dyes; Electron Transport; Magnetic Resonance Spectroscopy; Spectrometry, Fluorescence
PubMed: 37262973
DOI: 10.1016/j.saa.2023.122946 -
Toxics Aug 2023Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent...
Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear. This study aimed to elucidate the antioxidative effects of MFA and their underlying mechanisms. We observed that MFA treatment upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Treatment with various anthranilic acid derivative-class NSAIDs, including MFA, increased the expression of sequestosome 1 (SQSTM1) in HepG2 cells. MFA disrupted the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, activating the Nrf2 signaling pathway. SQTM1 knockdown experiments revealed that the effect of MFA on the Nrf2 pathway was masked in the absence of SQSTM1. To assess the cytoprotective effect of MFA, we employed tert-Butyl hydroperoxide (tBHP) as a ROS inducer. Notably, MFA exhibited a protective effect against tBHP-induced cytotoxicity in HepG2 cells. This cytoprotective effect was abolished when SQSTM1 was knocked down, suggesting the involvement of SQSTM1 in mediating the protective effect of MFA against tBHP-induced toxicity. In conclusion, this study demonstrated that MFA exhibits cytoprotective effects by upregulating SQSTM1 and activating the Nrf2 pathway. These findings improve our understanding of the pharmacological actions of MFA and highlight its potential as a therapeutic agent for oxidative stress-related conditions.
PubMed: 37755745
DOI: 10.3390/toxics11090735 -
Luminescence : the Journal of... Jul 2024Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain...
Mefenamic acid, renowned for its analgesic properties, stands as a reliable choice for alleviating mild to moderate pain. However, its versatility extends beyond pain relief, with ongoing research unveiling its promising therapeutic potential across diverse domains. A straightforward, environmentally friendly, and sensitive spectrofluorometric technique has been developed for the precise quantification of the analgesic medication, mefenamic acid. This method relies on the immediate reduction of fluorescence emitted by a probe upon interaction with varying concentrations of the drug. The fluorescent probe utilized, N-phenyl-1-naphthylamine (NPNA), was synthesized in a single step, and the fluorescence intensities were measured at 480 nm using synchronous fluorescence spectroscopy with a wavelength difference of 200 nm. Temperature variations and lifetime studies indicated that the quenching process was static. The calibration curve exhibited linearity within the concentration range of 0.50-9.00 μg/mL, with a detection limit of 60.00 ng/mL. Various experimental parameters affecting the quenching process were meticulously examined and optimized. The proposed technique was successfully applied to determine mefenamic acid in pharmaceutical formulations, plasma, and urine, yielding excellent recoveries ranging from 98% to 100.5%. The greenness of the developed method was evaluated using three metrics: the Analytical Eco-scale, AGREE, and the Green Analytical Procedure Index.
Topics: Mefenamic Acid; Fluorescent Dyes; Spectrometry, Fluorescence; Humans; Molecular Structure; Pharmaceutical Preparations; Limit of Detection
PubMed: 38956814
DOI: 10.1002/bio.4819 -
ACS Applied Bio Materials Oct 2023A tripodal amine (TPA) with -OH, N, and S donors is synthesized to functionalize a core-shell carbon dot composite (FCDs@SiO-TPA) for sensing application. The TPA is...
A tripodal amine (TPA) with -OH, N, and S donors is synthesized to functionalize a core-shell carbon dot composite (FCDs@SiO-TPA) for sensing application. The TPA is characterized by spectroscopic and spectrometric techniques, and the composite is characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectra (EDS) techniques. The composite has the ability to recognize mefenamic acid (MFA) selectively even in the presence of other drugs like ibuprofen sodium, acetylsalicylic acid, naproxen sodium, diclofenac sodium, and ketoprofen. It can also be used for the quantification of MFA by recording the emission quenching response of the sample at λ = 350 nm and λ = 460 nm (linear range = 1-8 μM and LOD = 197 nM). The density functional theory calculations and H NMR titration suggest quenching of the emission signal due to photoinduced electron transfer via hydrogen bonding between the probe and MFA. The composite FCDs@SiO-TPA has been demonstrated as a reliable and cost-effective sensing probe for the detection of MFA in pharmaceutical formulations, water samples, and cow urine samples.
Topics: Mefenamic Acid; Carbon; Spectroscopy, Fourier Transform Infrared; Silicon Dioxide; Biomass; Drug Compounding
PubMed: 37766456
DOI: 10.1021/acsabm.3c00597