家兔恒速静滴氟尿嘧啶时血药浓度的昼夜规律

Circadian rhythm of plasma 5-fluorouracil level during 24-h continuous venous infusion at a constant rate in rabbits

对9只新西兰兔进行恒速持续静滴氟尿嘧啶24小时,其间每隔3小时取静脉血少许备用,经高效液相色谱法测定血样本中的氟尿嘧啶浓度,并对血药浓度系列作方差分析和Cosinor分析。实验结果显示在恒速持续静滴5-FU过程中血药浓度随时间变化,且平均血浆5-FU浓度符合昼夜节律变化规律。高峰估计值在13时,低谷估计值在1时。

Preclinical experiments revealed that although the plasma concentration of 5-fluorouracil was at a 'stable state' by continuous infusion at a constant rate, circadian rhythm did exist. This experiment was made to observe whether the variation of plasma of 5-Furs level during 24-h continuous venous infusion in a circadian pattern existed in rabbits or not. The result might be useful in clarifying the chronophar macology of 5-FUrs. 5-FUrs was administrated to 9 New Zealand white rabbits by continuous venous infusion at a constant rate during a period of 24hrs. The dose for each rabbit was 40mg dissolved in 100ml normal saline and the infusion rate was 8.3 ml/hr. Plasma samples were collected 2hrs after administration at 10, 16, 19, 22, 1, 4, 7 o'clock. The animals were housed under normal light conditions. The 5-FUrs plasma concentration experienced variance and Cosinor analyses. A circadian rhythm was observed in plasma consentration of 5-FUrs of 9 rabbits (p<0.01,Cosinor analysis). Under normal conditins, the highest and lowest plasma concentration of 5-FUrs was 18.46μmol/L at 13 o'clock and 10.82μmol/L at 1 o'clock (F=13.16,P=0.02)repectively. Since no intersubject defferences in 24-hr mean plasma concentration were shown, the date were also expressed as percentages of analysis which also demonstrated a circadian rhythm with a double amplitude (p<0.01, total extent of variance) of 50% of the 24-hr mean and acrophase detected at 13 o'clock (the estimated peak time). Such findings might provide reference to the chronophar- macology of anticancer drugs when a continuous infusion schedule is designed. A circadian modulation of the infusion rate of 5-FUra could help to enhance therapeutic effects.