Effects of the plasma concentration of 5-fluorouracil and the duration of continuous venous infusion of 5-fluorouracil with an inhibitor of 5-fluorouracil degradation on Yoshida sarcomas in rats.
Effects of the plasma concentration of 5-fluorouracil and the duration of continuous venous infusion of 5-fluorouracil with an inhibitor of 5-fluorouracil degradation on Yoshida sarcomas in rats.
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DOI：
10.1111/j.1349-7006.1989.tb02285.x
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发表时间：
1989-03
期刊：
影响因子：
--
通讯作者：
Shirasaka T
中科院分区：
文献类型：
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作者：
Fujii S;Shimamoto Y;Ohshimo H;Imaoka T;Motoyama M;Fukushima M;Shirasaka T
研究了血浆中5-氟尿嘧啶（5-FU）水平和5-FU持续输注时间与5-FU对大鼠吉田肉瘤的抗肿瘤活性的相关性。连续输注期间5-FU血浆水平的昼夜节律变化可通过3-氰基-2，6-二羟基吡啶（CNDP）治疗来预防，CNDP可强烈抑制5-FU降解。在正常大鼠中以1：10的摩尔比连续静脉输注2 - 30 mg/kg 5-FU 24 h后，血液中的5-FU水平与5-FU剂量成线性比例。发现对大鼠吉田肉瘤的抗肿瘤活性的最佳方案是连续6天输注5 mg/kg的5-FU，持续24 h，使血浆5-FU水平为176 ng/ml。从肿瘤细胞植入后第5天开始连续6天输注5-FU，使血浆水平达到300 ng/ml，此时肿瘤重量约为1.0 g，所有大鼠的肿瘤均完全消退。
The correlations of the 5‐fluorouracil (5‐FU) level in the plasma and the duration of continuous 5‐FU infusion with the antitumor activity of 5‐FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5‐FU during continuous infusion was prevented by treatment with 3‐cyano‐2,6‐dihydroxypyridine (CNDP), which strongly inhibits 5‐FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5‐FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5‐FU level in the blood was linearly proportional to the dose of 5‐FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5‐FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5‐FU level of 176 ng/ml. Continuous infusion of 5‐FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.