Publication: Journal of Clinical Pharmacology
Abstract
Cisplatin chemotherapy is commonly co-administered with 5-HT3 antagonist antiemetics, but the effect of different antiemetic choices on platinum pharmacokinetics was unclear. This study developed a population pharmacokinetic model incorporating both bound and unbound platinum in 33 cancer patients randomized to receive ondansetron, granisetron, or palonosetron alongside cisplatin, using Phoenix NLME software. Patients receiving ondansetron or granisetron showed substantially higher circulating unbound platinum exposure (331% and 114% increases, respectively) compared with those receiving palonosetron. The findings suggest palonosetron co-treatment may reduce the risk of cisplatin-induced kidney injury relative to other 5-HT3 antagonist antiemetics.
Author(s): Thompson LE, Ghimire A, Wen X, Kim C, Doherty CL, Buckley BT, Bowles DW, O'Bryant CL, Jaimes EA, Aleksunes LM, Joy MS.
Published: December 22, 2024
Phoenix NLME: Modeling Bound and Unbound Drug
Phoenix NLME modeled both bound and unbound platinum exposure in this cisplatin study, revealing how antiemetic choice can shift nephrotoxicity risk. Phoenix NLME is the engine behind population PK/PD modeling, combining the flexibility of code with the ease of a guided interface, part of a Phoenix platform that can be extended with third-party tools.
