Comparative bioavailability of two capsule formulations of mefenamic acid.

Abstract

Pharmacokinetic behavior of single dose of 2 mefenamic acid capsule formulations was studied in a randomized crossover design in 22 healthy male volunteers. Following ingestion of 250 mg of either of the products, blood samples were obtained over a 14-hour period and the serum drug concentrations were determined by an HPLC assay with ultraviolet detection at 280 nm. The parametric 90% confidence intervals of the mean value of the ratio (fendol (test)/ponstan (reference)) of pharmacokinetic parameters were 0.88-1.07, 0.94-1.19, and 0.89-1.16 for AUC zero-infinity, Cmax and T1/2. In each case values were within the acceptable bioequivalence range of 0.8-1.25. Distribution-free point estimate for the difference in expected medians of Tmax of the 2 formulations (fendol-ponstan) was -0.5 hours with a 90% confidence interval of -1.0 to -0.25 which overlaps with the stipulated bioequivalence range of +/-0.48. The kinetic parameters a comparable to what is reported for mefenamic acid and there were no statistically significant differences in any of them when comparing the 2 products by ANOVA on log-transformed data. Although the 2 products are not equivalent regarding the secondary parameter Tmax, still the data indicate that they could be considered bioequivalent regarding rate of absorption (Cmax), extent of absorption (Cmax and AUC), and elimination (t1/2).