Pharmacokinetic boosting can be a strategy to enhance osimertinib exposure and reduce treatment associated costs. The OSIBOOST trial demonstrated that it was feasible to boost low osimertinib plasma trough levels with cobicistat. The current study aims to establish the equivalent dose of cobicistat boosted osimertinib compared to osimertinib 80 mg once daily (QD) by population pharmacokinetic (popPK) modeling.
View Article and Find Full Text PDFEur J Drug Metab Pharmacokinet
July 2024
Background And Objective: Several population pharmacokinetic (popPK) studies have been reported that can guide the prediction of osimertinib plasma concentrations in individual patients. It is currently unclear which popPK model offers the best predictive performance and which popPK models are most suitable for nonadherence management and model-informed precision dosing. Therefore, the objective of this study was to externally validate all osimertinib popPK models available in the current literature.
View Article and Find Full Text PDFIntroduction: Brain metastases (BM) are common in patients with advanced -mutated (m+) NSCLC. Despite good BM-related outcomes of osimertinib, several patients still experience intracranial progression. A possible explanation is pharmacologic failure due to low plasma trough levels (C) and consequently limited intracranial osimertinib exposure.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
December 2023
Recently, two small molecular inhibitors (SMIs) -adagrasib and sotorasib- have been introduced for targeting Kirsten rat sarcoma (KRAS) p.G12C mutations in patients with non-small cell lung cancer (NSCLC). In order to support pharmacokinetic research as well as clinical decision making, we developed and validated a simple and accurate liquid chromatography-tandem mass spectrometry method for the multiplexed quantification of adagrasib and sotorasib.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
June 2020
Thiosulfate sulfurtransferase (TST, EC 2.8.1.
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