tolfenamic acid / Generic mfg. - LARVOL DELTA

Antipyretic and Antinociceptive Activities of Tri-Phol-That Extract and Its Flavonoids: In Vivo and In Silico Evidence. (PubMed, ACS Omega) - "The hydroethanolic extract lowered rectal temperature in a dose-dependent manner, with maximum inhibition occurring at 100-200 mg/kg, although the effect was less potent than that of tolfenamic acid...Thus, it can be concluded that the extract of Tri-Phol-That had strong antipyretic and analgesic effects via multi-target inhibition of COX-1, COX-2, and mPGES-1, possibly due to the combined effects of rutin, quercetin, and kaempferol. These results support the traditional medicinal use of this extract and provide justification for further investigation as a phytotherapeutic agent."

Journal • Preclinical • Pain

COF-mediated tumor microenvironment-responsive platform and prodrug activation for combined chemo-sonodynamic cancer therapy. (PubMed, J Mater Chem B) - "Tolfenamic acid-based prodrug was stabilized by disulfide bonds and loaded into a covalent organic framework (COF) with a high loading efficiency of 39.2 wt%. Under a weak acid tumor microenvironment, the prodrug was released and activated by glutathione (GSH). Singlet oxygen (1O2) and hydroxyl radicals (˙OH) were efficiently generated under ultrasound irradiation, and excellent antitumor efficacy was achieved by combined chemo-sonodynamic therapy."

Biomarker • Journal • Oncology

Pharmacokinetics and Bioavailability of Tolfenamic Acid in Calves: First Evaluation of Subcutaneous Administration. (PubMed, Vet Med Sci) - "These findings demonstrate that SC administration of TA in calves results in prolonged but reduced systemic exposure compared with IM administration. The results support the need for route-specific dosing considerations and provide a basis for further studies on residue depletion and determination of withdrawal period in food-producing calves."

Journal • PK/PD data

Unexpected Effect of Digestion Products of Infant Formula in Enhancing the Solubilisation of Tolfenamic Acid During Digestion. (PubMed, Pharmaceutics) - "In those studies, digestion of the triglycerides in infant formula to produce more polar lipids, namely fatty acids and monoglycerides, produced a high-capacity solubilisation environment for weakly basic drugs such as clofazimine, driven mainly by ion-pairing of the fatty acid with the drug. The quantity of tolfenamic acid that was solubilised during digestion correlated approximately linearly with the quantity of free fatty acids produced during digestion. These results show that a weakly acidic drug can also exhibit digestion-driven solubilisation in a lipid-based formulation in the absence of ion-pairing and highlights the need to better understand drug response to digestion of lipid-based foods and formulations, and their versatility as a formulation option even for poorly water-soluble acidic drugs."

Journal • Gastrointestinal Disorder

Pharmacokinetics of Flunixin and Tolfenamic Acid in Experimental Endotoxemic Awassi Sheep. (PubMed, Vet Med Sci) - "The altered pharmacokinetics of flunixin and tolfenamic acid in endotoxemic sheep suggest that dose adjustments and careful therapeutic monitoring are necessary to maintain efficacy and safety."

Journal • PK/PD data

Comparison of the effects of remazolam and midazolam on the incidence of delirium following general anesthesia in patients undergoing elective non- cardiac major surgery: A prospective, randomized controlled study (ChiCTR) - P=N/A | N=86 | Recruiting | Sponsor: The Third Affiliated Hospital Sun Yat-sen University; The Third Affiliated Hospital Sun Yat-sen University

New trial • Anesthesia • CNS Disorders

Evaluation of Anti-Cancer Activity of Copper-Tolfenamic Acid Against Ovarian Cancer Cells (ISGE 2026) - "Conclusions Cu-TA demonstrates enhanced anti-cancer activity compared to TA by targeting Sp1 and Survivin in ovarian cancer cells. These findings highlight Cu-TA as a promising therapeutic candidate, warranting further in vivo and translational evaluation."

Gynecologic Cancers • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BIRC5

The pharmacokinetics of tolfenamic acid in Himalayan Griffon vultures. A better understanding for the safety of the drug in Old World vultures. (PubMed, Environ Toxicol Pharmacol) - "Given the more limited changes in UA, toxicity appears to resulted from altered renal perfusion, a known side effect of TA, rather than UA transporter inhibition as seen with DF. This would likely explain why the long T1/2 did not result in more substantial toxicity."

Journal • PK/PD data

Analgesic interventions in surgically castrated beef calves: impacts on biomarkers, thermography, and growth performance under tropical conditions. (PubMed, Trop Anim Health Prod) - "Forty-two intact Blanco Orejinegro (BON) calves were randomly assigned to three protocols: spermatic cord block with lidocaine plus tolfenamic acid (T1), low epidural anesthesia with lidocaine plus tolfenamic acid (T2), or tolfenamic acid alone (T3)...In contrast, significant temporal effects were observed, with cortisol decreasing at 48 h, haptoglobin peaking at 48-72 h, and IRT values increasing between 24 and 48 h postcastration. These results indicate that the time after castration, rather than the analgesic protocol, was the primary driver of physiological responses."

Biomarker • Journal • Anesthesia • Hematological Disorders • Pain • HP

Safety Assessment of Repeated Oral Administration of Tolfenamic Acid in Japanese Quails: Haematological, Biochemical and Histopathological Evaluations. (PubMed, Vet Med Sci) - "These findings indicate that tolfenamic acid administration does not adversely affect haematological or biochemical parameters. Although biochemical parameters remained normal, histopathological changes such as tissue damage may indicate early or subclinical injury that could impair organ function over time. These microscopic alterations might lead to long-term health issues in quails, even without biochemical abnormalities. Therefore, cautious dosing and regular tissue monitoring are important when using tolfenamic acid."

Journal • Hematological Disorders

Machine learning analysis of oral solid dosage formulation solubility variations by adjusting pressure and temperature. (PubMed, Sci Rep) - "This study helps pharmaceutical and chemical companies predict tolfenamic acid solubility and SC-CO2 density. The proposed models and ChOA hyper-parameter optimization solve solubility and density prediction problems in research and industry."

Journal

In vitro dynamic and quantitative monitoring of strigolactone-signaling complex formation by time-resolved FRET. (PubMed, Plant J) - "In addition, we found that tolfenamic acid, an antagonist of the SL receptor, inhibited the SL-induced PPI but could not disrupt the already-formed signaling complex. The TR-FRET system was also used to rapidly and specifically detect naturally occurring SLs from root exudates containing many impurities. This work provides insights into the molecular mechanism of SL perception as well as a powerful tool for activity-based screening of SL signaling modulators."

Journal • Preclinical • Targeted Protein Degradation

Crystal Morphology and Associated Face-Specific Growth Kinetics of Tolfenamic Acid as a Function of Its Solution Crystallization Environment. (PubMed, Cryst Growth Des) - "This is in contrast to the capping faces, which is found to be less well-defined with mass transfer and surface integration being more balanced depending on the degree of solution supersaturation. The interplay between solvent-dependent surface interactions and intermolecular packing with the crystal face-specific growth kinetics is highlighted, contributing well toward the development of a predictive framework for the design and control of the solid-form properties of organic materials."

Journal

Pluripotent Cinnamic Acid and Valproic Acid Hybrid Molecules Designed as Strong Anti-inflammatory and Anti-hyperlipidemic Compounds. (PubMed, Med Chem) - "The multiple activities of the synthesized compounds may serve for the manipulation of conditions involving inflammation and lipid deregulation, or the further optimization and production of compounds towards these ailments."

Journal • Cardiovascular • Dyslipidemia • Inflammation • Metabolic Disorders

COX-2 targeting Ru-arene complexes from metal-ligand synergistic enhancement strategy for breast cancer therapy. (PubMed, J Inorg Biochem) - "Toxic Ru-tol was synthesized from the non-toxic precursors aryl ruthenium azide and tolfenamic acid...Ru-tol demonstrated supeior penetration capacity and antiproliferative efficacy in 3D multicellular tumor spheroids (MCTS), suggesting the potent clinical applications. This work not only demonstrated the efficiency of MLSE strategy for the development of novel anti-cancer metal-based drugs, but also presented a promising target for the TNBC treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • MMP9 • PTGS2

Pharmacokinetics of Tolfenamic Acid Administered Orally and Intravenously at Different Doses in Pekin Ducks (Anas platyrhynchos domestica). (PubMed, Animals (Basel)) - "In ducks, tolfenamic acid's plasma protein binding was 99.74%, unaffected by concentration. These results may contribute to the application of tolfenamic acid in ducks at different doses, but dose-related changes in therapeutic efficacy should also be demonstrated."

Journal • PK/PD data

Pregnancy rate after treatment with a nonsteroidal anti-inflammatory drug (tolfenamic acid) at the time of embryo transfer in recipient cows. (PubMed, Theriogenology) - "Additionally, NSAID treatment improved pregnancy rates in recipients receiving in vitro-produced embryos at the morula stage (P = 0.05) but not at the early to expanded blastocyst stages (P = NS). In conclusion, we suggest that TA may provide reproductive benefits under specific ET situations, particularly in heifers and recipients with physiological or embryonic conditions commonly associated with reduced fertility."

Journal • Inflammation

Mechanistic investigation of methadone, tolfenamic acid, and cilnidipine in traumatic brain injury: a novel multi-target perspective outcome of network pharmacology. (PubMed, Inflammopharmacology) - "This study identified a primary target for MTD such as NOS1, NOS2, NOS3, DRD2, DAT (SLC6A3), MPO, SLC6A4, CXCR4-C-X-C, AKT1, SLC/8A2, HTR1A; for TA: MAPK1, GRIN1 and for CLD: IGF1R, DRD2, SHH, MAP2K1, CACNA1D, HTR2A, PDE4D, CASP3, MTOR, FASN, PTGS2, SCN9N, CNR1, CACNA1C, ABCB1, PIK3CA, GSK3B in the mechanistic regulation of TBI by reducing the activation of several pathways linked to development of TBI."

Journal • CNS Disorders • Vascular Neurology • ABCB1 • CASP3 • CXCR4 • DRD2 • FASN • HTR2A • MAP2K1 • MAPK1 • NOS1 • NOS2 • NOS3 • PACERR • PIK3CA • PTGS2 • SLC6A3 • SLC6A4

NSAIDS AS MODULATORS OF CATION CHANNELS: FENAMATES REPURPOSING IN CHANNELOPATHIES. (PubMed, ChemMedChem) - "In this review, we describe the ability of fenamates (i.e. niflumic, flufenamic, mefenamic, meclofenamic and tolfenamic acids) to differentially modulate the activity of cationic ion channels. Overall, preclinical and clinical studies suggest that fenamates represent a promising class of compounds for drug repurposing and for the development of new molecules, offering novel therapeutic opportunities for patients affected by ion channel-related disorders."

Journal • Cardiovascular • CNS Disorders • Epilepsy • Oncology • Pain

Pleiotropic Effects of the NSAID Fenamates on Chloride Channels: Opportunity for Ion Channelopathies? (PubMed, Pharmacol Res Perspect) - P=N/A, P1/2 | "This narrative review resumes the effects of niflumic acid (NFA), flufenamic acid (FFA), mefenamic acid (MFA), meclofenamic acid (MCFA), and tolfenamic acid (TFA) on different types of chloride channel. Therefore, thanks to their variegated modulatory activity on chloride channels, fenamates might be considered promising lead compounds for the development of new drug candidates that can target these altered channels involved in channelopathies. Trial Registration: EudraCT number: 2021-000708-39; ClinicalTrials.gov identifier: NCT029930005 and NCT02429570."

Journal • Review • CNS Disorders • Cystic Fibrosis • Epilepsy • Genetic Disorders • Immunology • Lysosomal Storage Diseases • Metabolic Disorders • Ophthalmology • Otorhinolaryngology • Pulmonary Disease • Rare Diseases • Respiratory Diseases

Characterization of feline nonsteroidal anti-inflammatory drug activated gene-1 (fNAG-1) and its protective function in kidney cells. (PubMed, BMC Vet Res) - "This study highlights the significant role of NAG-1 in feline kidney cells, revealing its high expression in the liver and kidney and demonstrating its protective effects on kidney function. These results underscore the potential of NAG-1 as a key factor in kidney protection. Future research should focus on further elucidating the molecular pathways involved and exploring therapeutic strategies to harness NAG-1 for managing obesity-related renal dysfunction in cats."

Journal • Genetic Disorders • Nephrology • Obesity • Renal Disease • BAX • GDF15

Non-covalent binding of non-steroidal anti-inflammatory drugs to antibiotics: preparation, characterization, physicochemical properties and study of single crystals of tolfenamic acid-enrofloxacin drug-drug salt and their antibacterial and anti-inflammatory activities. (PubMed, Int J Pharm) - "The in vitro antimicrobial activity and anti-inflammatory activity of TA-ENR were also somewhat improved compared to TA and ENR. The success of this work implies that we may provide new ideas for designing and synthesizing solid drugs with better physicochemical properties and bioactivity, as well as for the treatment of septic arthritis, through the formation of drug-drug co-crystals/salts."

Journal • Immunology • Rheumatology

Pharmacokinetic Characteristics of Tolfenamic Acid in Freshwater Crocodiles (Crocodylus siamensis). (PubMed, Animals (Basel)) - "Good bioavailability levels and favorable plasma concentrations of TA were obtained in freshwater crocodiles after IM administrations, considering that this is the preferred route of drug administration in freshwater crocodiles. Multi-dose and pharmacodynamic studies are needed to better establish the safety and efficacy of using TA in this crocodilian species."

Journal • PK/PD data

Local Antimicrobial Potential of Bupivacaine and Tolfenamic Acid-Loaded Ultra-High Molecular Weight Polyethylene (UHMWPE) for Orthopedic Infection. (PubMed, Bioengineering (Basel)) - "For the dual drug-loaded UHMWPE, the drug release rate from BP/TA combinations was interestingly not a direct function of the loaded drug weight percent, potentially due to the hydrophobicity of TA and the interactions between the two drugs. Combinations of BP and TA at the higher total drug concentration (10 and 20%) showed a prolonged antibacterial effect against S. aureus, with great potential for prophylactic use."

Journal • Infectious Disease • Orthopedics • Pain

Ru(II)-Fenamic-Based Complexes as Promising Human Ovarian Antitumor Agents: DNA Interaction, Cellular Uptake, and Three-Dimensional Spheroid Models. (PubMed, Inorg Chem) - "Cancer resistance to chemotherapeutic agents such as cisplatin presents a significant challenge, leading to treatment failure and poor outcomes...Four Ru(II) complexes with fenamic acid derivatives were synthesized and characterized: [Ru(L)(bipy)(dppp)]PF6, where L represents fenamic acid (HFen, complex 1), mefenamic acid (HMFen, complex 2), tolfenamic acid (HTFen, complex 3), and flufenamic acid (HFFen, complex 4)...These complexes also altered cell morphology, reduced cell density, and inhibited colony formation in the A2780 cells. Staining assays indicated induced cell death and organelle damage, highlighting their potential as promising antitumor agents."

Journal • Oncology • Ovarian Cancer • Solid Tumor