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

Article Article scientifique Article Population Pharmacokinetics of Trametinib and Impact of Nonadherence on Drug Exposure in Oncology Patients as Part of the Optimizing Oral Targeted Anticancer Therapies Study eng 2024-06-11 2024-06-11 author Ravix Anne author Bandiera Carole 0000-0002-9996-3100 784063 author Cardoso Evelina 0000-0001-7446-4594 677541 Section des sciences pharmaceutiques (FARMA) author Lata Pedreira Adrian 877199 author Chtioui Haithem author Decosterd Laurent Arthur author Wagner Anna Dorothea 0000-0003-4728-7013 author Schneider Voirol Marie Paule 0000-0002-7557-9278 604314 Section des sciences pharmaceutiques (FARMA) author Csajka Chantal 0000-0002-0660-082X 657943 Section des sciences pharmaceutiques (FARMA) author Guidi Monia 0000-0002-6419-9317 762075 2193 10.3390/cancers16122193 38927898 2072-6694 PMC11201946 https://www.mdpi.com/2072-6694/16/12/2193 <p>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.</p> Medication adherence Oral anticancer therapy Population pharmacokinetics Simulations Trametinib Dewey 615 Swiss Cancer Research Foundation HSR-4077-11-2016 31 Section des sciences pharmaceutiques 17 false 1344 Adhésion thérapeutique et interprofessionnalité Cancers 16 12 ce75aa57-5247-4d9a-9a87-a0eca9c4d291 Article (Published version) Public Article_scientifique_from_unpaywall.pdf 1754370 application/pdf CC BY 47f9935893fb281e1e30b4bb6659b51b02f82936bc40e365b5cb7a315c8216de openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Population Pharmacokinetics of Trametinib and Impact of Nonadherence on Drug Exposure in Oncology Patients as Part of the Optimizing Oral Targeted Anticancer Therapies Study	Cancers			2024	77	348

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