Talniflumate (oral chow; 0.4 mg/g; 21 days) dramatically enhanced survival in CF mice from 26% to 77%. It does not alter crypt goblet cell populations or modify intestinal expression of mCLCA3 but tends to diminish crypt mucoid impaction [1].

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Talnifluamate exerts its analgesic and anti‑inflammatory activity in the body through conversion to niflumic acid. The more potent analgesic activity of Talnifluamate compared to niflumic acid may be related to the significantly higher plasma niflumic acid concentration observed at 30 min after oral administration of Talnifluamate tablets (1.67 ± 0.54 μg/ml) versus niflumic acid tablets (0.38 ± 0.15 μg/ml) (p < 0.05). [1]
Talnifluamate has been reported to show lower ulcerogenic activity and toxicity while exhibiting greater anti‑inflammatory activity than niflumic acid (based on previous reports cited in the paper). [1]

Animal/Disease Models: CF mice with distal intestinal obstruction syndrome (DIOS)[1]
Doses: 0.4 mg/g
Route of Administration: oral; 21-day
Experimental Results: Distal intestinal obstruction syndrome cystic fibrosis mouse model The survival rate is improved.

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Absorption, Distribution and Excretion
Following a single oral administration in 12 subjects, the mean total plasma clearance of the major metabolite, niflunic acid, was 45 ml/min, with a mean volume of distribution of 0.12 l/kg. The drug exhibits a significant first-pass effect. Metabolism/Metabolites Primarily metabolized by the liver. Biological Half-Life The biological half-life in the 12 subjects was approximately 2 hours.

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Following oral administration of Talnifluamate tablets (740 mg, equivalent to 504 mg niflumic acid) to healthy male volunteers, Talnifluamate is rapidly absorbed and undergoes extensive first‑pass biotransformation to niflumic acid. Plasma Talnifluamate concentrations were below the detection limit (0.1 μg/ml) in 2 out of 5 subjects; in the remaining 3 subjects, detectable but low levels were observed. [1]
The partition coefficient (n‑octanol/pH 7.4 phosphate buffer) of Talnifluamate is 524.2, which is much higher than that of niflumic acid (82.3), indicating higher lipophilicity and potentially faster gastrointestinal absorption. [1]
Pharmacokinetic parameters of niflumic acid derived after Talnifluamate administration (mean, SE, n=5): AUC = 2212 (384) μg·min/ml; Cmax = 5.7 (0.3) μg/ml; tmax = 168.6 (18.0) min; MRT = 425.4 (47.9) min; elimination half‑life (t1/2) = 229.4 (24.5) min. No statistically significant differences (p < 0.05) were found in any of these parameters compared to niflumic acid tablets, except for the 30‑min concentration. [1]
After oral administration of Talnifluamate tablets (504 mg as niflumic acid equivalent), only 4 mg of niflumic acid was recovered in urine over 24 hours, suggesting extensive further metabolism (hydroxylation or glucuronidation) and/or saturation of renal excretion. Renal clearance of niflumic acid varied with plasma concentration: 9 ml/min/kg at plasma level 0.5 μg/ml (exceeding glomerular filtration rate of ~4 ml/min/kg), and decreased to less than 1 ml/min/kg at 6 μg/ml, indicating involvement of secretion and reabsorption processes. [1]

Protein Binding
Niflumate (the active form of Talniflumate) is a weak acid with a strong binding affinity to plasma proteins. A study of 12 volunteers showed that its bioavailability was 100%. It is a weak acid with a strong binding affinity to plasma proteins.

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Talnifluamate is reported to be less irritant to the gastrointestinal mucosa than niflumic acid (based on previous reports cited in the paper). [1]
Talnifluamate has been reported to show lower ulcerogenic activity and toxicity compared to niflumic acid (based on previous reports cited in the paper). [1]

[1]. Pharmacokinetics of talniflumate, a prodrug of niflumic acid, following oral administration to man. Archives of Pharmacal Research volume 19, Article number: 297 (1996).

[2]. Agonist and Antagonist Activities on Human NPFF(2) Receptors of the NPY Ligands GR231118 and BIBP3226. Br J Pharmacol.2001 May;133(1):1-4.

2-[3-(trifluoromethyl)aniline]-3-pyridinecarboxylic acid (3-oxo-1H-isobenzofuran-1-yl) ester belongs to the benzofuran class of compounds. Taniflurane is an anti-inflammatory molecule that has been studied and used as a mucin modulator for the treatment of cystic fibrosis, chronic obstructive pulmonary disease (COPD), and asthma. It is also used to treat inflammatory diseases such as rheumatoid arthritis. A Phase I clinical trial of taniflurane for the treatment of cystic fibrosis and COPD was completed in August 2001, and a Phase II clinical trial conducted in Ireland has been discontinued. Taniflurane has been approved for use in Argentina and other countries (excluding the United States, Europe, and Japan) for approximately 20 years.

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Drug Indications
Taniflurane is a phthalate ester of nifumiic acid with potent analgesic and anti-inflammatory effects, widely used to treat inflammatory diseases such as rheumatoid arthritis and osteoarthritis, and has also been studied for the treatment of cystic fibrosis.
Taniflurane is a phthalate ester of nifumiic acid with potent analgesic and anti-inflammatory effects, widely used to treat inflammatory diseases such as rheumatoid arthritis and osteoarthritis, and has also been studied for the treatment of cystic fibrosis.
Mechanism of Action Taniflurane is a potent and selective inhibitor of the core mucin synthase GCNT3 (core 2β-1,6 N-acetylglucosamine transferase). Taniflurane reduces GCNT3 gene expression and mucin production in vivo and in vitro. It enhances the efficacy of gefitinib (a chemotherapy drug) in pancreatic tumors. Taniflurane is a potent calcium-activated chloride channel (CaCC) blocker. Pharmacodynamics Taniflurane is metabolized to the prodrug niflurane, which has multiple pharmacodynamic effects. First, it blocks mucin synthesis. Second, taniflurane helps relieve pain and inflammation by blocking prostaglandin synthesis through cyclooxygenase.

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Talnifluamate (molecular weight = 414.3) is a prodrug of niflumic acid, synthesized by esterification of the carboxyl group of niflumic acid with a phthalidyl moiety. It is marketed as tablets (Somalgen) and prescribed for rheumatoid diseases. The usual dose of niflumic acid is 250 mg three times daily. Talnifluamate 370 mg is equivalent to 252 mg niflumic acid. [1]
In this study, five healthy male volunteers (age 23‑25 years, weight 68.2 ± 0.43 kg, height 173.4 ± 2.32 cm) participated. The study design was a single‑dose, two‑period crossover with a one‑week washout period. Subjects fasted for 12 h before and 4 h after drug administration. Each tablet was taken with 200 ml tap water. Blood samples were collected at pre‑dose and at 30, 60, 90, 120, 180, 210, 240, 360, 480, 600, and 1440 min post‑dose. [1]

C21H13F3N2O4

414.3341

414.082

66898-62-2

48229

White to yellow solid powder

1.5±0.1 g/cm3

534.6±50.0 °C at 760 mmHg

165-167ºC

277.1±30.1 °C

0.0±1.4 mmHg at 25°C

1.625

5.59

1

9

5

30

644

0

FC(C1C([H])=C([H])C([H])=C(C=1[H])N([H])C1=C(C([H])=C([H])C([H])=N1)C(=O)OC1([H])C2=C([H])C([H])=C([H])C([H])=C2C(=O)O1)(F)F

ANMLJLFWUCQGKZ-UHFFFAOYSA-N

InChI=1S/C21H13F3N2O4/c22-21(23,24)12-5-3-6-13(11-12)26-17-16(9-4-10-25-17)19(28)30-20-15-8-2-1-7-14(15)18(27)29-20/h1-11,20H,(H,25,26)

2-[[3-(Trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic acid 1,3-dihydro-3-oxo-1-isobenzofuranyl ester

BA7602-06BA 7602-06BA-7602-06

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~62.5 mg/mL (~150.85 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)