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

ABSTRACT: Effective inhibitors of invasion and metastasis represent a serious unmet clinical need. We have recently identified 4-fluoro-3',4',5'-trimethoxychalcone or C16 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 effect

SUBMITTER: Mus LM 

PROVIDER: S-EPMC5823406 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature