Area Under the Concentration-Time Curve of 15 Minute Intravenous Infusion Fluorouracil in Thai Colorectal Cancer Patients

Abstract

The aim of this study was to determine area under the concentration-time curve and pharmacokinetic of 5-fluorouracil (5-FU) in Thai colorectal cancer patients received 15 minute infusion of 5-FU 425 mg/m2/day. This is a prospective unicenter trial at Rajavithi Hospital. Patients who participated in this study, received folinic acid 20 mg/m2/day followed by 5-FU 425 mg/m2/day intravenous infusion in 15 minutes consequently for 5 days every 28 days. Blood samples were collected in the first day of cycle at 0, 5, 10, 15, 20, 30, 60 and 90 min after the beginning of 5-FU infusion. 5-FU plasma concentrations were determined by using HPLC method. Twenty-four patients enrolled in this study, 16 were men and 8 were women. The mean age ± SD was 55.3±14.5 years old. Six patients had TNM staging 2 cancer, nine had stage 3 cancer and nine had stage 4 cancer. Two patients had performance status 0, 15 patients had status 1 and 8 had status 2. Nine patients had metastases to lymph node , four had metastases to liver , three had metastases to lung, two had metastases to appendix and one had metastases to rectum . Most patients were collected blood samples of 1st and 3rd cycle of 5-FU therapy. As calculated by trapezoidal rule, average AUC was 415.2 ± 121.80mg/L.min (95% CI = 363.65-466 .20 mg/L.min). There were 2 patients had grade 1 and 4 patients had grade 2 hematological toxicity, no diarrhea , hand-foot syndrome and oral mucositis had been reported after monitored by completed blood cell count and interview in next follow up. Mean± SD of maximum concentration, observe clearance, volume of distribution and elimination constant were 18.04 ± 5.33 mg/L, 1.72 ± 0.69 L/min, 23.05±8.85 L and 0.08 ± 0.03 min-1, respectively.