Steady‐state Disposition of Diflunisal: Once‐ versus Twice‐daily Administration

To evaluate the steady‐state bioequivalence of the nonsteroidal antiinflammatory analgesic agent, diflunisal, administered once versus twice daily, 13 healthy volunteers received diflunisal as follows: (1) 1000 mg at 8:00 am and (2) 500 mg at 8:00 am and 8:00 pm, each for 14 days in a randomized crossover study. The mean (± SD) steady‐state peak plasma concentrations were significantly greater after once‐daily dosing (186 ± 25 μg/ml vs 150 ± 37 μg/ml; p < 0.01). The time to peak concentration was also longer after the single‐dose regimen (2.5 ± 0.8 vs 1.9 ± 0.9 hr; p < 0.05). The regimens were similar with respect to the mean 24‐hour area under the plasma concentration‐time curve at steady state (2839 ± 612 vs 2782 ± 778 μg·hr·ml −1 ), steady‐state plasma concentrations (118 ± 25 vs 116 ± 32 μg/ml), trough plasma concentration (85 ± 27 vs 92 ± 28 μg/ml) as well as 24‐hour urinary excretion (776 ± 79 vs 771 ± 89 mg) of diflunisal. Based on urinary recoveries, the bioequivalence ratio (once vs twice daily) was 1.01 ± 0.08. These results indicate that diflunisal administered once daily might offer comparable therapeutic effects but be more convenient than a twice‐daily regimen.