Summary of - Inhibition of cytochrome p450 enzyme and drug-drug interaction potential of acid reducing agents used in management of CDK inhibitors for breast cancer chemotherapy

Document Type

Article

Abstract

Study Background: Concurrent usage of proton pump inhibitors with palbociclib and ribociclib has been found to be affecting the progression free survival in the clinical setup.

Research goal and Objective: The study aimed to investigate the mechanism and magnitude of the drug-drug interaction between CDK 4/6 inhibitors and proton pump inhibitors.

Methodological approach :

  1. The interaction potential of proton pump inhibitors and CDK 4/6 inhibitors was predicted using molecular docking and metabolic stability assay in human liver microsomes.
  2. In vitro half-maximal inhibitory concentration (IC50) of proton pump inhibitors was determined.

Results and Discoveries :

  1. Proton pump inhibitors alter the conformation of the CYP3A4 and CYP2C19 enzymes and interact with their heme-prosthetic groups.
  2. Omeprazole and rabeprazole both significantly block midazolam's 1′-hydroxylation by CYP3A4 in vitro, with IC50 values of 9.86μM and 9.71μM, respectively.
  3. Further they also affected the metabolic clearance and in vitro half-life of palbociclib and ribociclib when co-incubated in human liver microsomes at concentration of 30μM.

Conclusion: Proton pump inhibitors such as rabeprazole and omeprazole exhibit the potential to cause clinically significant drug-drug interactions with palbociclib and ribociclib. Hence, it is suggested to use caution when prescribing proton pump inhibitors with this therapy.

Publication Date

February 2022

Recommended Citation

Patil PH, Jagadish PC, Fatima F, Birangal S, Shenoy GG, Rao M, Farooqui J, Rastogi H, Sharma T, Pinjari J. Inhibition of cytochrome P450 enzyme and drug-drug interaction potential of acid reducing agents used in management of CDK inhibitors for breast cancer chemotherapy. Current Drug Metabolism. 2022 Feb 1;23(2):137-49.

DOI/Link : https://doi.org/10.2174/1389200223666220218090948

Publication Date

2022

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