Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2017 Dec;83(12):2718-2728.
doi: 10.1111/bcp.13395. Epub 2017 Sep 20.

Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects

Sebastián Videla  1 , Mounia Lahjou  2 , Anna Vaqué  1 , Mariano Sust  1 , Mercedes Encabo  1 , Lluis Soler  1 , Artur Sans  1 , Eric Sicard  3 , Neus Gascón  1 , Gregorio Encina  1 , Carlos Plata-Salamán  1
Affiliations
Clinical Trial

Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects

Sebastián Videla et al. Br J Clin Pharmacol. 2017 Dec.

Abstract

Aims: Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination.

Methods: Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer-generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg).

Results: Thirty-six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 263, 346 and 349 ng ml-1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml-1 (mean cumulative area under the plasma concentration-time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml-1 ; 2183, 3093 and 2856 ng h ml-1 ; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported.

Conclusion: PK parameters of each API in CTC were modified by co-crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination.

Keywords: celecoxib; co-crystal; pain; pharmacokinetics; tramadol.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Study design. Treatment 1, 2 × 100 mg CTC tablets; Treatment 2, 2 × 50 mg IR tramadol capsules; Treatment 3, 1 × 100 mg celecoxib capsule; Treatment 4, 100 mg tramadol (2 × 50 mg IR capsules) plus 100 mg celecoxib (1 × 100 mg capsule). CTC, co‐crystal of tramadol–celecoxib; IR, immediate release
Figure 2
Figure 2
Mean plasma concentration vs. time profiles for tramadol following a single dose of CTC (Treatment 1), tramadol alone (Treatment 2) or the open combination of tramadol and celecoxib (Treatment 4). CTC, co‐crystal of tramadol–celecoxib
Figure 3
Figure 3
Mean plasma concentration vs. time profiles for M1 following a single dose of CTC (Treatment 1), tramadol alone (Treatment 2) or the open combination of tramadol and celecoxib (Treatment 4)]. CTC, co‐crystal of tramadol–celecoxib
Figure 4
Figure 4
Mean plasma concentration vs. time profiles for celecoxib following a single dose of CTC (Treatment 1), celecoxib alone (Treatment 3) or the open combination of tramadol and celecoxib (Treatment 4). CTC, co‐crystal of tramadol–celecoxib
See this image and copyright information in PMC

References

    1. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SPH, et al The IUPHAR/BPS guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucl Acids Res 2016; 44: D1054–D1068. - PMC - PubMed
    1. Alexander SPH, Davenport AP, Kelly E, Marrion N, Peters JA, Benson HE, et al The Concise Guide to PHARMACOLOGY 2015/16: G protein coupled receptors. Br J Pharmacol 2015; 172: 5744–5869. - PMC - PubMed
    1. Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, et al The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol 2015; 172: 6024–6109. - PMC - PubMed
    1. International Association for the Study of Pain . Declaration of Montréal. Declaration that access to pain management is a fundamental human right. 2010. Available at http://www.iasp‐pain.org/DeclarationofMontreal?navItemNumber=582 (last accessed 09 August 2016). - PubMed
    1. International Association for the Study of Pain (IASP), European Federation of IASP Chapters . Factsheet 4A: unrelieved pain is a major global healthcare problem. 2005. Available at http://www.iasp‐pain.org/files/Content/ContentFolders/GlobalYearAgainstP... (last accessed 09 August 2016).

Publication types

MeSH terms