Tolfenamic acid

261.7

261.70

237-264-3

3G943U18KM

757873

DTXSID1045409

C87328

M - Musculo-skeletal system

2922499990

49.3

5.2

Solid

1.3±0.1 g/cm3

207-207.5 °C

405.4°C at 760 mmHg

199.0±27.3 °C

1.658

soluble in water (slightly), acetone (~10 mg/ml), DMSO (52 mg/ml at 25°C), methanol (~10 mg/ml) and ethanol (50 mg/ml).

Refrigerator

2.66E-07mmHg at 25°C

5.11None

5.11

155.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|153.7 Ų [M+H]+ [CCS Type: TW]

6.1

UN 2811 6.1/PG 3

3

22

CB2687500

Xn

Stable at normal temperatures and pressures.

P301 + P310

H301

|Danger|H301 (97.73%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 132 companies from 2 notifications to the ECHA C&L Inventory.

Tolfenamic acid has a relatively low acute toxicity with LD50 values in 200-1000 mg/kg. The metabolites of tolfenamic acid are reported to have an even less important toxicity. Some of the expected toxicity is related to the presence of gastrointestinal effects such as gut ulceration and renal papillitis.

Tolfenamic acid presents high protein binding properties reaching 99.7% of the administered dose. Studies have studied the changes in protein binding depending on the presence of certain disorders that modify the dialysis equilibrium. These studies verify that modifications in blood creatinine, urea and bilirubin can significantly alter the concentration of unbound tolfenamic acid. The main binding structure is predicted to be related to lipid membrane structures.

In the information for tolfenamic acid, it is stated that this drug, being an NSAID, is effective in treating the pain associated with the acute attack of migraines in adults.

Studies have shown that tolfenamic acid presents a non-dose dependent partial inhibition of irritant-induced temperature rise as well as a dose-dependent inhibition of skin edema. By studying its NSAID properties more closely, it was noted a dose-related inhibition of serum thromboxane which indicated the inhibition of COX-1. In the same line, there was noted a inhibition of prostaglandin E2 synthesis which marks a related COX-2 inhibition. The maximal inhibition of thromboxane was greater than 80% as well as is proven to be a potent prostaglandin E inhibitor.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (See all compounds classified as Calcium Channel Blockers.)|Compounds capable of relieving pain without the loss of CONSCIOUSNESS. (See all compounds classified as Analgesics.)|Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. (See all compounds classified as Serotonin Antagonists.)|Compounds that inhibit the action of prostaglandins. (See all compounds classified as Prostaglandin Antagonists.)

Tolfenamic acid pharmacokinetic is marked by a short tmax of 0.94-2.04 h. It also presented a linear pharmacokinetic profile with an AUC from 13-50 mcg/ml.h if administered in a dose of 2-8 mg/kg respectively. The oral absorption is delayed and it gives a mean lag-time to absorption of 32 min. The peak plasma concentration of 11.1 mcg/ml. The bioavailability of tolfenamic acid is around 75%.|Tolfenamic acid is cleared relatively fast and it undergoes by hepatic metabolism where the produced metabolites are renally cleared as glucuronic acid conjugates. Most of the elimination occurs by extrarenal mechanisms in which the unchanged drug together with its glucuronide in urine accounts for only 8.8% of the administered dose.|The volume of distribution is of 1.79-3.2 L/kg. When tested intravenously, the reported steady-state volume of distribution was 0.33 L/kg.|The estimated clearance rate of tolfenamic acid is 0.142-0.175 L.h/kg. When tested intravenously, the reported clearance rate was 72.4 ml.h/kg.

The first pass metabolism accounts for 20% of the administered dose of tolfenamic acid. Urine metabolite studies have demonstrated the identification of five metabolites from which three of them are monohydroxylated, one is monohydroxylated and hydroxylated and one last metabolite that presented and oxidized methyl group to form a carboxyl group. Two of these hydroxylated metabolites are N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid and N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid.

The estimated half-life of tolfenamic acid is 8.01-13.50 hours. When tested intravenously, the reported half-life was 6.1h.

Tolfenamic acid inhibits the biosynthesis of prostaglandins, and it also presents inhibitory actions on the prostaglandin receptors. As commonly thought, the mechanism of action of tolfenamic acid is based on the major mechanism of NSAIDs which consists of the inhibition of COX-1 and COX-2 pathways to inhibit prostaglandin secretion and action and thus, to exert its anti-inflammatory and pain-blocking action. Nonetheless, some report currently indicates that tolfenamic acid inhibits leukotriene B4 chemotaxis of human polymorphonuclear leukocytes leading to an inhibition of even 25% of the chemotactic response. This activity is a not ligand specific additional anti-inflammatory mechanism of tolfenamic acid.

Bifenac

Human drugs -> Rare disease (orphan)|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan