A pilot study of 5-FU circadian pharmacokinetics in patients with nasopharyngeal carcinoma

Objective:While 5 FU was administered during day or night, its stead steady plasma concentration (Css) and toxicity of the regimens were compared so as to find out more effective administration of 5FU . Methods:A tolal of 18 patients randomly received CF plus 5 FU during day or night. 5 FU 1000 mg·(m 2·d) -1 was given by 8 hours continuous intravenously infusion ( IV ) for 5 days (d1～5 ), leucovorion 100 mg was administered after 5 FU infusion at 0,4,8 hour, together with carboplatin 300～350 mg/m 2,was administred IV on d6. Using HPLC method, plasma concentrationg of 5 FU were detected in 12 patients at 2,4,6,8 hour after 5 FU infusion. Results:Pharmacokinetics data showed although 5 FU was continuously infused at a constant rate, the Css of this drug varied in a circadian rhythmic manner, with maximal values occuring at 1AM. Area under concentration curve (AUC) of 5 FU at night was significantly higher than that during day. While CF flus 5 FU were administered at night, close positive correlation between 5 FU pharmacokinetics data (maximum Css, AUC) and the risk of mucositis were found. But in the daytime, these relationship was insignificant. No difference in toxicity was observed while CF flus 5 FU were administered during day or night at constant rate. Conclusion:It is suggested that toxicity of 5 FU may be related to its plasma concentration and sensitivity of target tissue. The optimal administration of 5 FU should be continuous IV, with peak between 3AM to 5AM,because it is helpful to avoid administration of 5 FU during its maximum plasma concentration and active DNA synthesis of oral mucosa.