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

Abstract

BackgroundCOX-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.ObjectivesThe 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.MethodsThis 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.ResultsThe 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.ConclusionsBased 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.

Acute Treatment of Migraine with Celecoxib Oral Solution: Results of a Randomized, Placebo-Controlled Clinical Trial

“…These enduring treatment effects were also demonstrated for the first attack and may reflect the relatively long half-life of DFN-15 (4.5 ± 1.6 hours). 14 …”

“…In healthy fasted adults, DFN-15 120 mg had a shorter T max than a 400 mg dose of celecoxib oral capsules (≤1 hour vs 2.5 hours) and a 44% greater relative bioavailability. 14 In a dose-ranging study comparing DFN-15 with placebo in the acute treatment of migraine, 15 a 120 mg dose (50 mg/mL) outperformed placebo and, because its efficacy was similar to DFN-15 240 mg, was chosen for further development. Development was guided by the hypotheses that a short T max would lead to rapid onset of treatment effects and that the lower dose would lead to improved GI safety and tolerability.…”

Celecoxib inhibits mitochondrial O2 consumption, promoting ROS dependent death of murine and human metastatic cancer cells via the apoptotic signalling pathway

“…The human equivalent dose (HED) based on the FDA guidelines for body area would be 16 mg/kg or 800mg/day for a 50 kg person. Recently, a liquid formulation of celecoxib (aka DFN-15) was developed which gave improved median time to peak concentration (Tmax) within 1 h whereas 2.5 h was required for the oral capsules[60]. The pharmacokinetics of DFN-15 was dose proportional over the range tested (120 to 240 mg) and the Cmax after administering DFN-15 at 120, 180, and 240 mg (1062-1933 ng/ml; 2.7 -5 µM) were much higher than for the 400mg oral capsules (611 ng/ml)[60].…”

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine with or without Aura

“…29 However, celecoxib capsules are slow to provide pain relief, with a median T max of 2.5 hours. 30 Because rapid pain relief is an important treatment goal, 30 , 31 and due to GI issues with oral NSAIDs, 30 celecoxib capsules have not been approved for the acute treatment of migraine in the U.S. 32 …”