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: 1000 mg at 8:00 AM and 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 micrograms/ml vs 150 +/- 37 micrograms/ml; p less than 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 less than 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 micrograms.hr.ml-1), steady-state plasma concentrations (118 +/- 25 vs 116 +/- 32 micrograms/ml), trough plasma concentration (85 +/- 27 vs 92 +/- 28 micrograms/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.
D000328:Adult; D001682:Biological Availability; D004061:Diflunisal / Q000008:administration & dosage / Q000097:blood* / Q000652:urine; D004334:Drug Administration Schedule; D006801:Humans; D007700:Kinetics; D008297:Male; D011897:Random Allocation; D012459:Salicylates / Q000097:blood*
D012459:Salicylates; D004061:Diflunisal