Pharmacokinetic – toxicodynamic Modeling to Elucidate the Involvement of Dorsal Root Ganglion Neuron in Oxaliplatin – induced Peripheral Neurpathu

Oxaliplatin-induced peripheral neuropathy limits dosing of this chemotherapy agent due to platinum accumulation and nerve cell damage in the dorsal root ganglion (DRG), but no effective management approach currently exists. This study administered repeated weekly doses of oxaliplatin to Wistar rats, measuring platinum concentrations in plasma and DRG tissue alongside neuropathy severity (via the von Frey test), and developed a pharmacokinetic-toxicodynamic model using Phoenix WinNonlin. Platinum accumulated in the DRG in a dose-dependent manner with repeated dosing, and the resulting PK-TD model, incorporating a DRG compartment, adequately predicted the time course of neuropathy severity. The model demonstrates the potential of DRG-based PK-TD modeling to help optimize oxaliplatin dosing strategies that reduce peripheral neuropathy risk.