Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium.

Meclofenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) approved for use in arthritis (osteo and rheumatoid), analgesia (mild to moderate pain), dysmenorrhea, and heavy menstrual blood loss (menorrhagia). At least three different biochemical effects have been defined for meclofenamic acid. It is a potent inhibitor of the enzyme cyclooxygenase, thereby inhibiting the production of prostaglandins. It also inhibits the release of 5-HETE and LTB4 from human neutrophils stimulated with calcium ionophore and antagonizes the response of tissues to certain prostaglandins. These mechanisms may explain in part the pharmacological profile and clinical effectiveness of this compound. The rapid onset of activity of meclofenamic acid and its duration of action may be the result of its pharmacokinetic profile. Sodium meclofenamate is completely bioavailable from capsules relative to an oral suspension dosage form. Maximum meclofenamic acid plasma concentrations are achieved in 0.5-2 h following doses of capsules. Meclofenamic acid is extensively metabolized. One of the metabolites, metabolite 1, is approximately 20% as active as the parent compound in inhibiting cyclooxygenase activity in vitro. This metabolite accumulates in plasma during repeated dosing. It is possible that this metabolite may contribute to at least some of the activity observed following administration of sodium meclofenamate.