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The bioavailabilities of five commercially available flufenamic acid (FA) capsules were studied in humans and beagle dogs. The dissolution rates of these capsules were determined by several methods. Experiments on in vitro/in vivo and humans/dogs correlations were performed to evaluate the dissolution test methods and the values of beagle dogs as models for predicting bioavailability of weak acid drugs in humans. Significant differences in the rates and extents of bioavailability of the different capsules were observed both in humans and dogs, but results in humans differed from those in dogs. The dissolution rates, determined by dissolution methods involving pretreatment with acidic solutions, correlated significantly with bioavailabilities in humans and dogs; however, those obtained by the rotating basket and paddle methods without any surface active agents did not correlate with in vivo data.

Flufenamic acid (200 mg) was administered in the form of a soft capsule to 8 young healthy volunteers after an overnight fast. The drug was absorbed irregularly and plasma curves showed large variation. Peak plasma concentrations varied strongly (6-20 micrograms/ml) but were usually reached within 1.5 h. The terminal elimination half-life is long (5-22 h) and the total body clearance is low (80-150 ml/min) causing long mean residence time (4-28 h). The total apparent volume of distribution is much larger than the total body water volume. The large intersubject variations led to the conclusion that mean values of the pharmacokinetic parameters of flufenamic acid after oral administration are not useful for practical purposes.