Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral administration of S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil.
Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral administration of S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil.
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DOI：
10.1038/sj.bjc.6601224
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发表时间：
2003-09-01
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
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比较了口服二氢嘧啶脱氢酶（DPD）抑制氟嘧啶S-1与长时间静脉输注5-氟尿嘧啶（5-FU）的药代动力学和药效学。总共有10例胃癌患者接受了5- fu的PVI治疗，剂量为250 mg m−2 day−1，持续5天。在9天的洗脱期后，患者每天接受两次分次给药，持续28天。S-1分别于上午9时和19时口服。在体表面积（BSA）小于1.25 m2的患者中，S-1的日剂量为80 mg day -1，在BSA大于或等于1.25 m2至小于1.5 m2的患者中，S-1的日剂量为100 mg day -1，在BSA大于或等于1.5 m2的患者中，S-1的日剂量为120 mg day -1。测定5-FU和F-β-丙氨酸（FBAL）的血浆浓度进行药代动力学分析，并在5-FU的PVI和口服S-1的1-5天监测血浆尿嘧啶浓度作为DPD抑制的替代标志物（药效学分析）。第5天5- fu的曲线下面积（AUC0-10 h） 5- fu的PVI为728±113 ng h ml−1，S-1为1364±374 ng h ml−1。5-FU的AUC0-10 h 5-FU PVI: S-1比值中位数为1.9。5- fu治疗PVI第5天FBAL的AUC0-10 h为9465±3225 ng h ml -1，而S-1治疗第5天的AUC0-10 h为1725±605 ng h ml -1。第5天尿嘧啶的AUC0-10 h与5- fu的PVI分别为252±60 ng h ml -1和12 582±3060 ng h ml -1。与5-FU的PVI相比，S-1组FBAL的AUC0-10 h明显降低，血浆尿嘧啶浓度显著升高，明显显示了DPD抑制的作用。
The pharmacokinetics and pharmacodynamics of oral S-1, a dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine, were compared with those of protracted venous infusion (PVI) of 5-fluorouracil (5-FU). In all, 10 patients with gastric cancer received PVI of 5-FU at a dose of 250 mg m−2 day−1 for 5 days. After a washout period of 9 days, the patients received two divided doses daily for 28 days. S-1 was administered orally at about 0900 and 1900 hours. The daily dose of S-1 in terms of tegafur was 80 mg day−1 in patients with a body surface area (BSA) of <1.25 m2, 100 mg day−1 in those with a BSA of ⩾1.25 m2 to <1.5 m2, and 120 mg day−1 in those with a BSA of ⩾1.5 m2. Plasma concentrations of 5-FU and F-β-alanine (FBAL) were measured for pharmacokinetic analysis, and the plasma uracil concentration was monitored as a surrogate marker of DPD inhibition (pharmacodynamic analysis) in the same patients on days 1–5 of PVI of 5-FU and on days 1–5 of oral S-1. The area under the curve (AUC0–10 h) of 5-FU on day 5 was 728±113 ng h ml−1 for PVI of 5-FU and 1364±374 ng h ml−1 for S-1. The median 5-FU PVI : S-1 ratio of the AUC0–10 h of 5-FU was 1.9. The AUC0–10 h of FBAL on day 5 of PVI of 5-FU was 9465±3225 ng h ml−1, AUC0–10 h, as compared with 1725±605 ng h ml−1 on day 5 of S-1 treatment. The AUC0–10 h of uracil on day 5 was 252±60 ng h ml−1 with PVI of 5-FU and 12 582±3060 ng h ml−1 with S-1. The AUC0–10 h of FBAL was markedly lower and plasma uracil concentrations were significantly higher for S-1 than for PVI of 5-FU, clearly demonstrating the effect of DPD inhibition.
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影响因子：
45.3
作者：
Mani, S;Hochster, H;Lokich, J
通讯作者：
Lokich, J
影响因子：
45.3
作者：
van Groeningen, CJ;Peters, GJ;Giaccone, G
通讯作者：
Giaccone, G
影响因子：
45.3
作者：
Budman, DR;Meropol, NJ;Griffin, T
通讯作者：
Griffin, T
影响因子：
8.4
作者：
Chollet, P;Schöffski, P;Fumoleau, P
通讯作者：
Fumoleau, P
影响因子：
45.3
作者：
Lévy, E;Piedbois, P;Erlichman, C
通讯作者：
Erlichman, C