Meclofenamic acid

Absorption

Rapidly absorbed in man following single and multiple oral doses with peak plasma concentrations occurring in 0.5 to 2 hours. The concomitant administration of antacids (aluminum and magnesium hydroxides) does not interfere with absorption of meclofenamic acid. Unlike most NSAIDs, which when administered with food have a decrease in rate but not in extent of absorption, meclofenamic acid is decreased in both. It has been reported that following the administration of meclofenamic acid capsules one-half hour after a meal, the average extent of bioavailability decreased by 26%, the average peak concentration (Cmax) decreased fourfold and the time to Cmax was delayed by 3 hours.

Toxicity

After a massive overdose, CNS stimulation may be manifested by irrational behavior, marked agitation and generalized seizures. Following this phase, renal toxicity (falling urine output, rising creatinine, abnormal urinary cellular elements) may be noted with possible oliguria or anuria and azotemia. A 24 year-old male was anuric for approximately one week after ingesting an overdose of 6 to 7 grams of meclofenamate sodium. Spontaneous diuresis and recovery subsequently occurred.

Chemical properties

White Crystalline Solid

Originator

Meclomen,Warner Lambert,US,1980

The Uses of Meclofenamic acid

Meclofenamic acid is used for the same conditions as flufenamic acid.

The Uses of Meclofenamic acid

Anti-inflammatory; antipyretic

Indications

For the relief of mild to moderate pain, for the treatment of primary dysmenorrhea and for the treatment of idiopathic heavy menstrual blood loss. Also for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis.

Background

A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.

What are the applications of Application

Meclofenamic Acid is An anti-inflammatory and antipyretic

Definition

ChEBI: An aminobenzoic acid that is anthranilic acid in which one of the hydrogens attached to the nitrogen is replaced by a 2,6-dichloro-3-methylphenyl group. A non-steroidal anti-inflammatory drug, it is used as the sodium salt for the treatment of dysmenorrhoe (painful periods), osteoarthritis and rheumatoid arthritis.

Manufacturing Process

A mixture consisting of 22.7 g potassium o-bromobenzoate, 16.6 g 2,6- dichloro-3-methylaniline, 12 ml N-ethylmorpholine, 60 ml diethylene glycol dimethyl ether, and 1.0 g anhydrous cupric bromide is heated in a nitrogen atmosphere at 145°C to 155°C for 2 hours. The reaction mixture is diluted with 60 ml diethylene glycol dimethyl ether and acidified with 25 ml concentrated hydrochloric acid. The acidic mixture is diluted with 100 ml of water and the liquid phase decanted from the insoluble oil. The insoluble oil is stirred with methanol and the crystalline N-(2,6-dichloro-3-methylphenyl) anthranilic acid which separates is collected and washed with methanol. The product, after recrystallization from acetone-water mixture, melts at 248°C to 250°C.

brand name

Meclomen (Parke-Davis, Portugal, USA), Meclodol (Parke Davis, Italy), Stadium (Menarini, Belgium).

Therapeutic Function

Antiinflammatory

Pharmacokinetics

Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals.

Clinical Use

Meclofenamat is a nonsteroidal anti-inflammatory drug used for the treatment of mild to moderate pain, musculoskeletal, and joint disorders like rheumatoid arthritis and osteoarthritis as well as dysmenorrhoea. Meclofenamate inhibits COX-1 and COX-2 and modifies ion channels.

Side Effects

Meclofenamic acid is available as its sodium salt hydrate. This drug is indicated for the relief of acute and chronic rheumatoid arthritis and osteoarthritis. Gastrointestinal distress, including diarrhea, nausea, vomiting, and abdominal pain, is the most commonly reported adverse effect.

Synthesis

Meclofenamic acid, N-(2,6-dichloro-m-tolyl)anthranylic acid (3.2.20), is synthesized analogous to flufenamic acid, by the reaction of potassium salt of 2-bromobenzoic acid with 2,6-dichloro-3-methylaniline in the presence of copper (II) bromide in a mixture of N-ethylmorpholine and diglyme [82,83].

Metabolism

Hepatic. Meclofenamic acid is extensively metabolized to an active metabolite (Metabolite I; 3-hydroxymethyl metabolite of meclofenamic acid) and at least six other less well characterized minor metabolites. Only Metabolite I has been shown in vitro to inhibit cyclooxygenase activity with approximately one fifth the activity of meclofenamic acid.