Summary of - Molecular Insights into the Mechanism of Modulatory Effects of Proton Pump Inhib-itors on P-glycoprotein Mediated Drug Transport of Palbociclib and Ribociclib

Document Type

Article

Abstract

Study Background: Palbociclib and ribociclib are substrates of efflux transporter P-glycoprotein which plays a key role in their absorption.

Research goal and Objective: The study investigated the role of P-glycoprotein in the interaction taking place between CDK inhibitors and PPIs affecting the absorption and pharmacokinetics of palbociclib and ribociclib.

Methodological approach :

  1. To predict the potential of proton pump inhibitors, to inhibit the P-glycoprotein mediated intestinal transport of palbociclib and ribociclib and investigate the molecular basis of interaction occurring, a combined approach of molecular docking and ex vivo everted gut sac model was used.

Results and Discoveries :

  1. It was observed that omeprazole and rabeprazole reduced the absorptive permeability of ribociclib by 1.76 and 2.54 folds and palbociclib by 3.04 and 1.26 folds, respectively, in ex vivo experiments.
  2. The ATP site of the nucleotide binding domain was found to be bound by omeprazole, rabeprazole, and pantoprazole, with binding energies of -27.53, -29.56, and -38.44 Kcal/mol, respectively.

Conclusion: Experiments conclude that proton pump inhibitors can inhibit P-glycoprotein, which can result in drug-drug interactions with palbociclib and ribociclib. Therefore, therapeutic drug monitoring is essential while proton pump inhibitors and cyclin-dependent kinase inhibitors are being co-administered.

Publication Date

June 2023

Recommended Citation

Desai MP, Harish Patil P, Vullendula SK, Birangal S, Shenoy GG, Rao M, Dengale SJ, Bhat K, Jagadish PC. Molecular Insights into the Mechanism of Modulatory Effects of Proton Pump Inhibitors on P-glycoprotein Mediated Drug Transport of Palbociclib and Ribociclib. Current Drug Metabolism. 2023 Jun 1;24(6):458-65.

DOI/Link : https://doi.org/10.2174/1389200224666230815122312

Publication Date

2023

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