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Group name EquipeCTCS
Item Type Journal Article
Title Liquid chromatography-tandem mass spectrometric assay for the quantification of CDK4/6 inhibitors in human plasma in a clinical context of drug-drug interaction
Creator Leenhardt et al.
Author Fanny Leenhardt
Author Matthieu Gracia
Author Catherine Perrin
Author Claudia Muracciole-Bich
Author Bénédicte Marion
Author Celine Roques
Author Marie Alexandre
Author Nelly Firmin
Author Stephane Pouderoux
Author Litaty Mbatchi
Author William Jacot
Author Alexandre Evrard
Abstract The CDK4/6 inhibitors palbociclib and ribociclib are kinase inhibitors used in association with hormonal therapy for the management of patients with metastatic breast cancer. Like most kinase inhibitors, therapeutic drug monitoring may be used for personalize their dosage. To this aim, we developed and validated a sensitive and specific HPLC-MS/MS method for palbociclib and ribociclib quantification in blood samples. We then quantified exposure to palbociclib (plasma trough concentration; Ctrough) in a real-life cohort of patients with locally invasive or metastatic breast cancer (n = 18) at day 15 of the first cycle of palbociclib treatment to characterize palbociclib concentration at steady state (Clinicaltrials.gov identifier NCT04025541, IdRCB n° 2018-A00064-51, 03/07/2018). The geometric mean (± standard deviation [min-max]) of palbociclib plasma Ctrough was 88.58 ng/mL (± 26.4 [46.5 ng/mL - 133 ng/mL]) at day 15. Some covariates, such as drug-drug interactions, could explain the concentration variations observed in our Caucasian cohort. These first results in real-life settings obtained with our HPLC-MS/MS method give important information on palbociclib monitoring and pharmacokinetic variability.
Publication Journal of Pharmaceutical and Biomedical Analysis
Volume 188
Pages 113438
Date 2020-09-05
Journal Abbr J Pharm Biomed Anal
Language eng
DOI 10.1016/j.jpba.2020.113438
ISSN 1873-264X
Library Catalog PubMed
Extra PMID: 32623316
Tags Benzimidazoles, Breast Neoplasms, CDK4/6 inhibitor, Chromatography, Liquid, cliniçc, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Drug Interactions, Drug-drug interactions, Female, HPLC-MS/MS, Humans, Pharmaceutical Preparations, Protein Kinase Inhibitors, Tandem Mass Spectrometry, Therapeutic drug monitoring
Date Added 2023/11/14 - 15:24:27
Date Modified 2023/11/14 - 15:42:54
Notes and Attachments PubMed entry (Attachment)
Version soumise (Attachment)


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