Comparative bioavailability of a dispersible formulation of diclofenac and finding of double plasma peaks.

We carried out a comparative study of the bioavailability of a typical, enteric-coated diclofenac with regard to a new dispersible formulation whose faster dissolution results in an earlier onset of its analgesic effect. This randomized, crossover study was conducted in 12 healthy male volunteers, who received in fasting 100 mg of enteric-coated diclofenac (Dolotrén, FAES) and 100 mg of dispersible diclofenac (Dolotrén Dispersable, FAES), with one-week interval between both. Blood samples were taken at pre-established times during the 24 hours after dosing, and plasma concentrations of diclofenac were determined by HPLC. Possible adverse experiences were monitored with a check-list, and blood and urinalysis were performed for safety assessment. The dispersible formulation showed a relative extent of bioavailability between 78% and 99% (90% CI) for the AUC0-infinity, being the 90% CI for the Cmax 63%-129%. The time to Cmax (Tmax) was significantly shorter with the dispersible than with the enteric-coated formulation (95% CI for the difference = 1.5-4.25 hours) as the T0(lag) or time to measurable plasma concentrations (1.9-4.2 hours, 95% CI). A relevant feature in the study was the finding of a second peak at 2-2.5 hours post-dosing in 7 out of 11 profiles of subjects receiving the dispersible formulation. Both formulations were well tolerated in clinical and laboratory terms. In conclusion, the new dispersible formulation of diclofenac allows absorption to begin more rapidly and plasma peak is reached earlier, a fact that may be relevant to the analgesic treatment of acute pain.

RCT Entities:   Population Interventions Outcomes