Abstract

510 Background: Pharmacokinetically (PK) guided dose adjustment of 5-fluorouracil (5-FU) has been reported better than body surface area based dosing of 5-FU. On the other hand, few articles have been reported about PK guided dose management of oral drug chemotherapy. The aim of this study is to assess the possibility of pharmacokinetically guided dose management of capecitabine with a nanoparticle antibody-based immunoassay for 5-FU (My5-FUR assay). Methods: Colorectal cancer patients receiving chemotherapy with FOLFOX, FOLFIRI, LV5FU2, Capecitabine, CapeOx (capecitabine plus oxaliplatin) were analyzed by My5-FUR assay. Blood samples were collected after 24 hours of 5-FU infusion or 2 hours after administration of capecitabine at day 7. Correlation between liquid chromatography-mass spectrometry (LC-MS) and My5-FUR assay of 5-FU were also examined. Results: A total of 50 patients were analyzed by My5-FUR assay. A linear relationship (r=0.9204) exists between LC-MS and My5-FUR assay. The area under the concentration curve of continuous 5-FU infusion were 15~56mg-h/L, and the concentrations of 5-FU after administration of capecitabine were 41~457 ng/mL. Severe side effects were observed in the patients with plasma concentration of 5-FU greater than 300 ng/mL 2 hours after administration of capecitabine. Conclusions: Plasma concentrations of 5-FU after administration of capecitabine were measurable by My5-FUR assay. The concentrations of 5-FU were lower in capecitabine than continuous 5-FU. The distribution of 5-FU was wider in capecitabine than continuous 5-FU. It is possible to manage dose of capecitabine pharmacokinetically.

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