Summary of - Differential effects of dietary polyphenols on oral pharmacokinetics of cyclin-dependent kinase inhibitors in rats: a mechanistic framework for in vitro–in vivo extrapolation

Document Type

Article

Abstract

Study Background: Cyclin-dependent kinase inhibitors exhibit low bioavailability due to its rapid first-pass metabolism and P-gp mediated intestinal efflux.

Research goal and Objective: The current study investigated the impact of dietary polyphenols on the oral pharmacokinetics of cyclin-dependent kinase inhibitors.

Methodological approach :

  1. An approach combining molecular docking; in vitro preclinical assay using rat liver microsomes and Caco-2 cell monolayers and in vivo, pharmacokinetic experiment was used to study the interaction.

Results and Discoveries :

  1. Commonly consumed dietary polyphenols curcumin and quercetin significantly inhibited both intestinal efflux and CYP3A4-mediated metabolism of palbociclib and ribociclib (p < 0.05).
  2. In rats pretreated with curcumin, Cmax of palbociclib exhibited a 5.13% increase, while the AUC0-24h of ribociclib showed a significant increase of 18.83% (p < 0.05).

Conclusions: The utilization of curcumin as a bioenhancer can enhance the bioavailability of dual substrates of P-gp and CYP3A4. Whereas, quercetin does not exhibit any bio enhancing activity specific to inhibition of P-gp and CYP3A4.

Publication Date

February 2024

Recommended Citation

Patil PH, Desai MP, Birangal S, Gautham Shenoy G, Jagadish PC. Differential effects of dietary polyphenols on oral pharmacokinetics of cyclin-dependent kinase inhibitors in rats: a mechanistic framework for in vitro–in vivo extrapolation. Journal of Pharmacy and Pharmacology. 2024 Feb 1;76(2):93-105.

DOI/Link : https://doi.org/10.1093/jpp/rgad115

Publication Date

2024

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