Estimation of CDK inhibitors by RP-HPLC: application for pharmacokinetic interactions studies with PPIs

Mrunal Pradeep Desai, Prajakta Harish Patil, Gurupur Gautham Shenoy, Jagadish Puralae Channabasavaiah*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The study investigated pharmacokinetic interactions between palbociclib and ribociclib with proton pump inhibitors (PPIs) using the reverse-phase high-performance liquid chromatography (RP-HPLC) method. Methods: Developed RP-HPLC method quantified palbociclib and ribociclib in biological matrices. In vitro metabolic stability assays and in vivo studies in rats evaluated effect of omeprazole and esomeprazole on pharmacokinetics of palbociclib and ribociclib. Results: The RP-HPLC method was sensitive, accurate and linear. Esomeprazole and omeprazole decreased metabolic clearance of palbociclib and ribociclib by several folds. In vivo, esomeprazole elevated Cmax of palbociclib and ribociclib by 90.1% and 86.4%, whereas omeprazole reduced it by 32.0% and 16.8%, respectively. Conclusion: The RP-HPLC method was used to analyze in vitro and in vivo samples. Long-term treatment with PPIs affects pharmacokinetics of palbociclib and ribociclib, necessitating optimal chemotherapy regimen.

Original languageEnglish
JournalBioanalysis
DOIs
Publication statusAccepted/In press - 2024

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • General Pharmacology, Toxicology and Pharmaceutics
  • Clinical Biochemistry
  • Medical Laboratory Technology

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