Meclofenamate drugs

Two compounds of the fenamate class of antiinflammatory drugs are marketed in the United States. Mefenamic acid (Ponstel) is indicated only for analgesia and primary dysmenorrhea when therapy will not exceed 1 week. Meclofenamate sodium (Meclomen) is prescribed for rheumatoid arthritis and osteoarthritis. 

Clinical use Meclofenamate (McLean and Geuckman, 1983) is a nonsteroidal anti-inflammatory drug used for the treatment of mild to moderate pain, musculoskeletal and joint disorders such as rheumatoid arthritis and osteoarthritis as well as dysmenorrhoea. 

Koup, J. R., Tucker, E., Thomas, D. J., Kinkel, A. W., Sedman, A. J., Dyer, R., Sharoky, M. A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium, Biopharm. Drug Dispos. 1990, 11, 1-15. 

The thromboxanes have a six-membered ring containing an ether. They are produced by platelets (also called thrombocytes) and act in the formation of blood clots and the reduction of blood flow to the site of a clot. The nonsteroidal antiinflammatory drugs (NSAIDs)— aspirin, ibuprofen, and meclofenamate, for example— were shown by John Vane to inhibit the enzyme prostaglandin H2 synthase (also called cyclooxygenase or COX), which catalyzes an early step in the pathway from arachidonate to prostaglandins and thromboxanes (Fig. 10-18 see also Box 21-2). 

Meclofenamate and mefenamic acid (Table 36-1) inhibit both COX and phospholipase A2. Meclofenamate appears to have adverse effects similar to those of other NSAIDs, though diarrhea and abdominal pain may be more common it has no advantages over other NSAIDs. This drug enhances the effect of oral anticoagulants. Meclofenamate is contraindicated in pregnancy its efficacy and safety have not been established for young children. 

In contrast to the above Deveaux method, Mehta and Schulman [37] described that the native fluorescence of mefenamic, flufenamic and meclofenamic acids is more useful for determination of these drugs compared to the fluorescence of the derivatives-substituted acridones and benzoxazines of these drugs by treatment with H2S04 and HCHO, respectively. The determination of mefenamic acid at trace level by fluorescence spectrometry was also reported by Miller et al. [38]. 

The use of second-derivative synchronous fluorescence spectrometry was reported by Ruiz et al. [42] to develop a simple, rapid and sensitive fluorimetric method for the determination of binary mixtures of the nonsteroidal antiinflammatory drugs flufenamic (FFA), meclofenamic (MCFA) and mefenamic (MFA) acids in serum and in pharmaceutical formulations. The method is based on the intrinsic fluorescence of these compounds in chloroform. A differential wavelength of 105 nm was used for the resolution of FFA-MFA and MFA-MCFA mixtures, whereas the FFA-MCFA mixture was determined at a differential wavelength of 40 nm. Serum samples were treated with trichloroacetic acid to remove the proteins, and the analytes were extracted in chloroform prior to determination. Pharmaceutical preparations were analyzed without prior separation steps. 

Giachetti et al. [60] compared the performance of mass selective detector (MSD), electron capture detector (ECD) and nitrogen-phosphorus detector (NPD) of gas chromatography systems in the assay of six nonsteroidal antiinflammatory drugs in the plasma samples. As a practical test, six NSAIDs (mefenamic, flufenamic, meclofenamic and niflumic acids, diclofenac and clonixin) added to plasma samples were detected and quantified. The analyses were carried out after solvent extraction from an acidic medium and subsequent methylation. The linearity of response was tested for all the detection systems in the range of 1-25 ng/mL. Precision and accuracy were detected at 1, 5 and 10 ng/mL. The minimum quantifiable level for the six drugs was about 1 ng/mL with each of the three detection systems. 

Antiinflammatory drugs, such as aspirin, naproxen, and meclofenamate are useful in relieving migraine attack. 

A list of retention times of anti-inflammatory compounds and other acidic drugs, relative to meclofenamic acid, is given in Table 6. 

Stabler I, Kapui Z, Ambrus J L1994 Study on the mechanisms of action of sodium meclofenamic acid (meclomen) a double inhibitor" of the arachidonic acid cascade. Journal of Medicine 25 371-382 Stillman M, Schlesinger P 1990 Nonsteroidal antiinflammatory drugs nephrotoxicity. Archives of Internal Medicine 150 268-270... 

Tobin T 1979 Pharmacology review the nonsteroidal antiinflammatory drugs II. Equiproxen, meclofenamic acid, fiunixin meglumine and others. Journal of Equine Medicine and Surgery 6 298-302... 

Mefenamic acid (Ponstel, Ponstan [United Kingdom], Dysman [United Kingdom]) and meclofenamate sodium [Meclomen] have been used mostly in the short-term treatment of pain in soft-tissue injuries, dysmenorrhea, and in rheumatoid and osteoarthritis. These drugs are not recommended for use in children or pregnant women. 

The pKa values of the N-arylanthranilic acids (4.0-4.2) resemble those of the arylalkanoic acids thus, it is not surprising that they are strongly bound to plasma proteins and that interactions with other highly protein bound drugs are very probable. The most common interactions reported are those of mefenamic acid and meclofenamic acid with oral anticoagulants. Concurrent administration of aspirin results in a reduction of plasma levels of meclofenamic acid. 

B gar FD, Smith TC. Drug interactiem studies with sodium meclofenamate (Meclomen ). Curr TherRes 91Z) 23 (April Suppl), S51-S59. 

In healthy subjects dextropropoxyphene 260 mg daily and sodium meclofenamate 400 mg daily for a week was found to have no effect on the plasma levels of either drug."... 

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