Publication: Journal of Pharmacology & Clinical Toxicology
Abstract
Cisplatin causes acute kidney injury in over 30% of patients, and incorporating a sensitive injury biomarker into pharmacokinetic modeling could improve understanding of this toxicity. This study developed a population pharmacokinetic/toxicodynamic (PK-TD) model incorporating plasma platinum and urinary kidney injury molecule-1 (KIM-1) concentrations in 39 cancer patients randomized to different 5-HT3 antagonist antiemetics alongside cisplatin, using Phoenix NLME software. Patients receiving ondansetron showed substantially higher platinum exposure and urinary KIM-1 levels (increases of 94-235%) compared with those receiving palonosetron, with previous cisplatin exposure and antiemetic choice identified as significant covariates. The findings suggest palonosetron co-treatment may reduce the risk of cisplatin-induced kidney injury as measured by this sensitive biomarker.
Author(s): Thompson LE, Ghimire A, Wen X, Kim C, Choza J, Doherty CL, Buckley BT, Bowles DW, O'Bryant CL, Pfister DG, Jaimes EA, Aleksunes LM, Joy MS
Published: September 20, 2024
Phoenix NLME: Linking Exposure to a Kidney Biomarker
Phoenix NLME built the PK-toxicodynamic model behind this cisplatin study, connecting platinum exposure directly to a sensitive kidney-injury biomarker. Phoenix NLME can be paired with Model Designer to select, configure, and simulate models directly in the browser, guided by an AI assistant, within a Phoenix platform relied on by more than 11,000 users worldwide.
