Population Pharmacokinetics of Trametinib and Impact of Nonadherence on Drug Exposure in Oncology Patients as Part of the Optimizing Oral Targeted Anticancer Therapies Study.

Details

Serval ID
serval:BIB_3DC9393D4173
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population Pharmacokinetics of Trametinib and Impact of Nonadherence on Drug Exposure in Oncology Patients as Part of the Optimizing Oral Targeted Anticancer Therapies Study.
Journal
Cancers
Author(s)
Ravix A., Bandiera C., Cardoso E., Lata-Pedreira A., Chtioui H., Decosterd L.A., Wagner A.D., Schneider M.P., Csajka C., Guidi M.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
11/06/2024
Peer-reviewed
Oui
Volume
16
Number
12
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Trametinib is a targeted therapy used for the treatment of solid tumours, with significant variability reported in real-life studies. This variability increases the risk of suboptimal exposure, which can lead to treatment failure or increased toxicity. Using model-based simulation, this study aims to characterize and investigate the pharmacokinetics and the adequacy of the currently recommended doses of trametinib. Additionally, the simulation of various suboptimal adherence scenarios allowed for an assessment of the impact of patients' drug adherence on the treatment outcome. The population data collected in 33 adult patients, providing 113 plasmatic trametinib concentrations, were best described by a two-compartment model with linear absorption and elimination. The study also identified a significant positive effect of fat-free mass and a negative effect of age on clearance, explaining 66% and 21% of the initial associated variability, respectively. Simulations showed that a maximum dose of 2 mg daily achieved the therapeutic target in 36% of male patients compared to 72% of female patients. A dose of 1.5 mg per day in patients over 65 years of age achieved similar rates, with 44% and 79% for male and female patients, respectively, reaching the therapeutic target. Poor adherence leads to a significant drop in concentrations and a high risk of subtherapeutic drug levels. These results underline the importance of interprofessional collaboration and patient partnership along the patient's journey to address patients' needs regarding trametinib and support medication adherence.
Keywords
medication adherence, oral anticancer therapy, population pharmacokinetics, simulations, trametinib
Pubmed
Web of science
Open Access
Yes
Create date
03/07/2024 8:13
Last modification date
06/07/2024 7:06
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