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

Clin Drug Investig. 2017 Oct;37(10):937-946. doi: 10.1007/s40261-017-0548-6.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Biological Availability
  • Capsules
  • Celecoxib / administration & dosage
  • Celecoxib / pharmacokinetics*
  • Cross-Over Studies
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Capsules
  • Cyclooxygenase 2 Inhibitors
  • Celecoxib