Mefenamic acid is a non-steroidal anti-inflammatory drug that inhibits hCOX-1, having IC50 values of 40 nM and 3 μM for hCOX-1 and hCOX-2, respectively [1]. Mefenamic acid (0-100 μM) is cytotoxic to KB, Saos-2, and 1321N cells; however, U-87MG cells are resistant [2].

Absorption, Distribution and Excretion
Mefenamic acid is rapidly absorbed after oral administration.
The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.3 The elimination half-life of mefenamic acid is approximately two hours. Mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys. Both renal and hepatic excretion are significant pathways of elimination.
1.06 L/kg [Normal Healthy Adults (18-45 yr)]
Oral cl=21.23 L/hr [Healthy adults (18-45 yrs)]
CROSSES PLACENTAL BARRIER IN MONKEYS...EXCRETED IN URINE, BILE &/OR FECES...
ABSORBED SLOWLY FROM GI TRACT...HIGH PERCENTAGE...BOUND TO PLASMA PROTEINS. PEAK PLASMA LEVELS APPEAR IN 2 TO 4 HR...ANALGESIA MAY PERSIST FOR UP TO 6 HR...ABOUT 50%...IS EXCRETED IN URINE WITHIN 24 HR /HUMAN, ORAL/

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Metabolism / Metabolites
Mefenamic acid undergoes metabolism by CYP2C9 to 3-hydroxymethyl mefenamic acid, and further oxidation to a 3-carboxymefenamic acid may occur. The activity of these metabolites has not been studied. Mefenamic acid is also glucuronidated directly.
MEFENAMIC ACID...IS TRANSFORMED TO HYDROXYMETHYL DERIVATIVE & TO ACID BY MAJOR, IF NOT ONLY, METABOLIC PATHWAY IN DOG, MONKEY, & HUMAN.
Mefenamic acid has known human metabolites that include 3-hydroxymethyl mefenamic aci.

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Biological Half-Life
2 hours
...ABOUT 50%...IS EXCRETED IN URINE WITHIN 24 HR /HUMAN, ORAL/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because there is little published experience with mefenamic acid during breastfeeding and it is potentially toxic, other agents may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
90%

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Interactions
...WARFARIN CAN BE DISPLACED FROM PLASMA PROTEIN BY MEFENAMIC ACID...INCR IN FREE WARFARIN CAN RANGE FROM 66-400% WITH CORRESPONDING INCR IN ANTICOAGULANT ACTION. BECAUSE OF DOSAGES INVOLVED, INTERACTIONS ARE MORE LIKELY TO BE IMPORTANT IN PT TREATED WITH WARFARIN THAN IN WORKERS WHO USE IT AS PESTICIDE...
EFFECTS OF ORAL ANTICOAGULANT AGENTS ARE ENHANCED.

[1]. Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. Biochem J. 1995 Jan 15;305 (Pt 2):479-84.

[2]. In Vitro Cytotoxic Effects of Celecoxib, Mefenamic Acid, Aspirin and Indometacin on Several Cells Lines. J Dent (Shiraz). 2016 Sep;17(3):219-25.

Mefenamic acid is an aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 2,3-dimethylphenyl group. Although classed as a non-steroidal anti-inflammatory drug, its anti-inflammatory properties are considered to be minor. It is used to relieve mild to moderate pain, including headaches, dental pain, osteoarthritis and rheumatoid arthritis. It has a role as an analgesic, an antirheumatic drug, a non-steroidal anti-inflammatory drug, an antipyretic, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor, an environmental contaminant and a xenobiotic. It is an aminobenzoic acid and a secondary amino compound.
A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.
Mefenamic acid is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of mefenamic acid is as a Cyclooxygenase Inhibitor.
Mefenamic Acid is an anthranilic acid and non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic and analgesic activities. Mefenamic acid inhibits the activity of the enzymes cyclo-oxygenase I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. The resulting decrease in prostaglandin synthesis, by prostaglandin synthase, is responsible for the therapeutic effects of mefenamic acid. Mefenamic acid also causes a decrease in the formation of thromboxane A2 synthesis, by thromboxane synthase, thereby inhibiting platelet aggregation.
A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.

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Drug Indication
For the treatment of rheumatoid arthritis, osteoarthritis, dysmenorrhea, and mild to moderate pain, inflammation, and fever.
FDA Label

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Mechanism of Action
Mefenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.

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Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors
MEFENAMIC ACID (PONSTEL) ... PROVIDES ANALGESIA IN MAN SIMILAR TO THAT PRODUCED BY ASPIRIN.
...INDICATED FOR RELIEF OF PAIN RESULTING FROM DENTAL EXTRACTIONS.
DRUG PREFERABLY SHOULD BE TAKEN WITH FOOD.
MEFENAMIC ACID SHOWED FAVORABLE RESULTS RELATIVE TO SOME ANALGESICS.

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Drug Warnings
SINCE IT IS NOT SUPERIOR TO ESTABLISHED ANALGESICS & CAN CAUSE SERIOUS TOXICITY, USE OF MEFENAMIC ACID IS NOT RECOMMENDED. IF IT IS USED, ADMIN SHOULD NOT BE EXTENDED BEYOND 7 DAYS. IF DIARRHEA OCCURS, DRUG MUST BE DISCONTINUED & NOT USED AGAIN. IT SHOULD NOT BE USED IN CHILDREN OR IN WOMEN OF CHILDBEARING AGE.
IT IS CONTRAINDICATED IN PT WITH ULCERATION OF UPPER OR LOWER INTESTINAL TRACT...& PT KNOWN TO BE HYPERSENSITIVE TO DRUG. ...CONSIDER ITS USE ONLY IN CASES WHICH EITHER CAN NOT TOLERATE OR DO NOT RESPOND TO LESS TOXIC AGENTS.
MEFENAMIC ACID IS CONTRAINDICATED IN PT...WITH IMPAIRED RENAL FUNCTION, & SHOULD BE USED WITH CAUTION IN ASTHMATICS BECAUSE IT MAY EXACERBATE CONDITION.
Maternal Medication usually Compatible with Breast-Feeding: Mefenamic acid: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/

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Pharmacodynamics
Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase.

C15H15NO2

241.29

241.11

61-68-7

Mefenamic acid-d4;1216745-79-7;Mefenamic Acid-d3;1189707-81-0;Mefenamic acid-13C6;1325559-19-0

4044

White to off-white solid powder

1.2±0.1 g/cm3

398.8±30.0 °C at 760 mmHg

230 °C

195.0±24.6 °C

0.0±1.0 mmHg at 25°C

1.639

5.33

2

3

3

18

292

0

HYYBABOKPJLUIN-UHFFFAOYSA-N

InChI=1S/C15H15NO2/c1-10-6-5-9-13(11(10)2)16-14-8-4-3-7-12(14)15(17)18/ h3-9,16H,1-2H3,(H,17,18)

2-(2,3-dimethylanilino)benzoic acid

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)

Solubility in Formulation 1: 2.5 mg/mL (10.36 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.36 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 25.0 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.)