Background & Objective: Because there are several mechanisms of activity and toxicity and inter-individual variation in pharmaco- dynamics of 5-fluorouracil (5-FU),it is difficult to predict the sensitivity and toxicity of 5-FU in an individual patient. This study was designed to assess inter-patient variation of 5-FU steady-state plasma concentration and the relationship of plasma concentration of 5-FU with toxic side effects and therapeutic response.
Methods: Twenty patients with nasopharyngeal carcinoma were treated with 5-FU combined with cisplatin(DDP). Blood samples were collected after 24 hours of infusion of 5-FU. Plasma concentrations of 5-FU were measured using high performance liquid chromatography(HPLC) with column temperature at 25 Celsius degree, flow rate at 1.3 ml/min, wave length at 260 nm and 1 mmol/l phosphate buffer (pH 3.0) as mobile phase.
Results: The plasma concentrations of 5-FU were normally distributed in the patients. No adverse effects were noted in the patients with plasma concentration of 5-FU lower than 600 microg/L, and severe toxic side effects were observed in the patients with plasma concentration of 5-FU greater than 1000 microg/L. The differences between plasma concentrations of 5-FU and each grade side effects reached statistical significance (P< 0.05).
Conclusion: The plasma concentration of 5-FU have highly inter-individual variation in the patients with nasopharyngeal carcinoma. Plasma concentrations of 5-FU were associated with the toxicity and treatment response.
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