Assessment of Oxaliplatin-induced Chronic Neuropathy and Anticancer Efficacy Through Pharmacokinetic and Toxicodynamic Evaluation of a Rat Model of Colorectal Cancer.

Abstract

Oxaliplatin-induced chronic neuropathy is a prominent factor for dose reduction and not completing all cycles of chemotherapy for patients with colorectal cancer (CRC). The aim of the study was to investigate the pharmacokinetics and toxicodynamics of oxaliplatin-induced chronic neuropathy in CRC rats to ensure effective management. A rat model of CRC was developed using 1,2-Dimethylhydrazine and dextran sulfate. Oxaliplatin (L-OHP) was administered intravenously to CRC rats every week. The pharmacokinetic profiles and tumor distribution of L-OHP and chronic neuropathies were investigated for over four weeks. The mean values of the area under the concentration-time curve for L-OHP showed a dose-dependent increase. Chronic neuropathy occurred from Day 14 in the 8 mg/kg group and Day 19 in the 3 and 5 mg/kg groups. These results provide preliminary information for the development of a pharmacokinetic and toxicodynamic model of L-OHP for CRC therapy cycles.