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Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers
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...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602059/ https://www.ncbi.nlm.nih.gov/pubmed/28748412 http://dx.doi.org/10.1007/s40261-017-0548-6 |
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author | Pal, Arindam Shenoy, Srinivas Gautam, Anirudh Munjal, Sagar Niu, Jing Gopalakrishnan, Mathangi Gobburru, Joga |
author_facet | Pal, Arindam Shenoy, Srinivas Gautam, Anirudh Munjal, Sagar Niu, Jing Gopalakrishnan, Mathangi Gobburru, Joga |
author_sort | Pal, Arindam |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5602059 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-56020592017-10-04 Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers Pal, Arindam Shenoy, Srinivas Gautam, Anirudh Munjal, Sagar Niu, Jing Gopalakrishnan, Mathangi Gobburru, Joga Clin Drug Investig Original Research Article 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. Springer International Publishing 2017-07-26 2017 /pmc/articles/PMC5602059/ /pubmed/28748412 http://dx.doi.org/10.1007/s40261-017-0548-6 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Article Pal, Arindam Shenoy, Srinivas Gautam, Anirudh Munjal, Sagar Niu, Jing Gopalakrishnan, Mathangi Gobburru, Joga Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers |
title | Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers |
title_full | Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers |
title_fullStr | Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers |
title_full_unstemmed | Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers |
title_short | Pharmacokinetics of DFN-15, a Novel Oral Solution of Celecoxib, Versus Celecoxib 400-mg Capsules: A Randomized Crossover Study in Fasting Healthy Volunteers |
title_sort | pharmacokinetics of dfn-15, a novel oral solution of celecoxib, versus celecoxib 400-mg capsules: a randomized crossover study in fasting healthy volunteers |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602059/ https://www.ncbi.nlm.nih.gov/pubmed/28748412 http://dx.doi.org/10.1007/s40261-017-0548-6 |
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