Schwartz P M, Turek P J, Hyde C M, Cadman E C, Handschumacher R E
Cancer Treat Rep. 1985 Jan;69(1):133-6.
To provide a model for pharmacokinetic studies in patients administered high iv doses of 5-FU after allopurinol or other modifiers of toxicity, rats were given radioactive 5-FU as an iv bolus. At a dose of 50 mg/m2 only 16% of circulating radioactivity was identified as 5-FU after 30 minutes, whereas greater than 90% of radioactivity was 5-FU when rats were given a 1800-mg/m2 dose. This 36-fold increase in 5-FU dose was associated with a greater than 150-fold increase in the 30-minute plasma concentration of 5-FU (0.02-3.3 mM). In patients, it was possible to increase the maximum tolerated dose of 5-FU given as a weekly rapid iv bolus from 800 to 1700 mg/m2 when a 3-day course of allopurinol (900 mg/day orally) preceded 5-FU administration. A dose-dependent increase in the apparent half-life of 5-FU in the plasma was observed and plasma concentrations at 30 minutes were as high as 500 microM after a 1600-mg/m2 dose of the drug.
为了建立一个在患者接受别嘌呤醇或其他毒性调节剂后静脉注射高剂量5-氟尿嘧啶（5-FU）时进行药代动力学研究的模型，给大鼠静脉推注放射性5-FU。在剂量为50mg/m²时，30分钟后循环放射性中只有16%被鉴定为5-FU，而当给大鼠1800mg/m²的剂量时，超过90%的放射性是5-FU。5-FU剂量增加36倍，与5-FU在30分钟时血浆浓度增加超过150倍（0.02 - 3.3mM）相关。在患者中，当在5-FU给药前给予3天疗程的别嘌呤醇（口服900mg/天）时，每周快速静脉推注5-FU的最大耐受剂量能够从800mg/m²增加到1700mg/m²。观察到血浆中5-FU的表观半衰期呈剂量依赖性增加，在给予1600mg/m²剂量的药物后，30分钟时血浆浓度高达500μM。
