Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers

摘要

Abstract Background COX-2 inhibitors can be effective for acute migraine, but none is supplied in a rapidly absorbed, ready-to-use oral liquid formulation. DFN-15, a novel oral liquid formulation of celecoxib, is being developed for the acute treatment of migraine with or without aura. Clinical studies with this formulation are ongoing. Objectives The objectives of the present study were to compare the bioavailability of DFN-15 with that of the commercial formulation of celecoxib 400-mg oral capsules (Celebrex ? ) and to determine the dose proportionality of DFN-15 in healthy fasted volunteers. Methods This single-dose randomized crossover study in 16 healthy fasted volunteers evaluated the pharmacokinetics and relative bioavailability of DFN-15 at doses of 120, 180, and 240?mg against the commercial formulation of celecoxib 400-mg oral capsules and determined the dose proportionality of DFN-15. Results The maximum observed plasma concentrations ( C max ) of celecoxib after the administration of DFN-15 120, 180, and 240?mg (1062–1933?ng/ml) were higher than for the 400-mg oral capsules (611?ng/ml). The median time to peak concentration ( T max ) was within 1?h for DFN-15 and 2.5?h for the oral capsules. The pharmacokinetics of DFN-15 were dose proportional from 120 to 240?mg. Partial area under the plasma concentration–time curves (AUCs) from 15?min to 2?h for DFN-15 120?mg were at least threefold higher than for the oral capsules, and the relative bioavailability of DFN-15 was approximately 140% that of the oral capsules. DFN-15 was well tolerated, with no new or unexpected adverse events. Conclusions Based on a faster rate of absorption and increased bioavailability, DFN-15 is being evaluated as an abortive medication for acute treatment in patients with migraine.