Advanced search
1 file | 6.57 MB

Vehicle development, pharmacokinetics and toxicity of the anti-invasive agent 4-fluoro-3’,4’,5’-trimethoxychalcone in rodents

Liselot Mus (UGent) , Geertrui Denecker (UGent) , Franki Speleman (UGent) and Bart Roman (UGent)
(2018) PLOS ONE. 13(2).
Author
Organization
Abstract
Effective inhibitors of invasion and metastasis represent a serious unmet clinical need. We have recently identified 4-fluoro-3',4',5'-trimethoxychalcone or C-16 as a potent anti-invasive molecule. In this paper, we report on the development of an optimized vehicle for oral administration of C16. We also explore its pharmacokinetic and toxicity profile in rodents as a prelude to a broad-scope evaluation as a pharmacological tool in animal models of disease. C16 showed suboptimal pharmacokinetics with limited oral bioavailability and whole blood stability. Rapid metabolism with elimination via glutathione conjugation was observed. An oral dosing routine using medicated gels was developed to overcome bioavailability issues and yielded sustained whole blood levels above the half maximal effective concentration (EC50) in a 7-day study. The compound proved well-tolerated in acute and chronic experiments at 300 mg/kg PO dosing. The medicated gel formulation is highly suitable for evaluation of C16 in animal models of disease.
Keywords
DIMETHYL SULFOXIDE, METASTASIS, CHALCONES, CANCER, DIMETHYLSULFOXIDE, PERSPECTIVE, MODELS, DRUGS

Downloads

  • journal.pone.0192548.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 6.57 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Mus, Liselot, Geertrui Denecker, Franki Speleman, and Bart Roman. 2018. “Vehicle Development, Pharmacokinetics and Toxicity of the Anti-invasive Agent 4-fluoro-3’,4',5'-trimethoxychalcone in Rodents.” Plos One 13 (2).
APA
Mus, L., Denecker, G., Speleman, F., & Roman, B. (2018). Vehicle development, pharmacokinetics and toxicity of the anti-invasive agent 4-fluoro-3’,4',5'-trimethoxychalcone in rodents. PLOS ONE, 13(2).
Vancouver
1.
Mus L, Denecker G, Speleman F, Roman B. Vehicle development, pharmacokinetics and toxicity of the anti-invasive agent 4-fluoro-3’,4',5'-trimethoxychalcone in rodents. PLOS ONE. 2018;13(2).
MLA
Mus, Liselot, Geertrui Denecker, Franki Speleman, et al. “Vehicle Development, Pharmacokinetics and Toxicity of the Anti-invasive Agent 4-fluoro-3’,4',5'-trimethoxychalcone in Rodents.” PLOS ONE 13.2 (2018): n. pag. Print.
@article{8551997,
  abstract     = {Effective inhibitors of invasion and metastasis represent a serious unmet clinical need. We have recently identified 4-fluoro-3',4',5'-trimethoxychalcone or C-16 as a potent anti-invasive molecule. In this paper, we report on the development of an optimized vehicle for oral administration of C16. We also explore its pharmacokinetic and toxicity profile in rodents as a prelude to a broad-scope evaluation as a pharmacological tool in animal models of disease. C16 showed suboptimal pharmacokinetics with limited oral bioavailability and whole blood stability. Rapid metabolism with elimination via glutathione conjugation was observed. An oral dosing routine using medicated gels was developed to overcome bioavailability issues and yielded sustained whole blood levels above the half maximal effective concentration (EC50) in a 7-day study. The compound proved well-tolerated in acute and chronic experiments at 300 mg/kg PO dosing. The medicated gel formulation is highly suitable for evaluation of C16 in animal models of disease.},
  articleno    = {e0192548},
  author       = {Mus, Liselot and Denecker, Geertrui and Speleman, Franki and Roman, Bart},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {DIMETHYL SULFOXIDE,METASTASIS,CHALCONES,CANCER,DIMETHYLSULFOXIDE,PERSPECTIVE,MODELS,DRUGS},
  language     = {eng},
  number       = {2},
  pages        = {23},
  title        = {Vehicle development, pharmacokinetics and toxicity of the anti-invasive agent 4-fluoro-3{\textquoteright},4{\textquoteright},5{\textquoteright}-trimethoxychalcone in rodents},
  url          = {http://dx.doi.org/10.1371/journal.pone.0192548},
  volume       = {13},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: