Pharmacokinetics of amifostine and its metabolites in the plasma and ascites of a cancer patient
Pharmacokinetics of amifostine and its metabolites in the plasma and ascites of a cancer patient
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DOI：
10.1007/s002800050553
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发表时间：
1996-11-01
影响因子：
3
通讯作者：
vanderVijgh, WJF
中科院分区：
文献类型：
--
作者：
Korst, AEC;Gall, HE;vanderVijgh, WJF
氨磷汀是一种抗化疗和放疗毒性的药物，本文研究了它在癌症患者血浆和腹水中的药代动力学。采用高效液相色谱法（HPLC）和电化学检测法测定氨磷汀、其活性代谢产物WR 1065和二硫化物（对称二硫化物和混合二硫化物）。氨磷汀和WR 1065均从血浆中快速清除（1小时内分别为峰浓度的95%和50%）。从WR 1065快速形成的二硫化物被清除得慢得多（最终半衰期为13.6 h）。多次给药导致WR 1065峰值水平增加和二硫化物峰值水平降低的趋势。仅1%的递送剂量出现在腹水中。因此，腹水或其他第三间隙的存在不会对氨磷汀的药代动力学产生影响。
The pharmacokinetics of amifostine, a protector against chemotherapy and radiation-induced toxicities, was investigated in the plasma and ascites of a cancer patient. A high-performance liquid chromatography (HPLC) procedure with electrochemical detection was used to measure amifostine, its active metabolite, WR 1065, and the disulfides (symmetrical plus mixed disulfides). Both amifostine and WR 1065 were rapidly cleared from the plasma (95% and 50% of the peak concentration within 1 h, respectively). The disulfides, which were rapidly formed from WR 1065, were cleared much more slowly (final half-life 13.6 h). Multiple dosing resulted in a tendency toward increasing peak levels of WR 1065 and decreasing peak levels of the disulfides. Only 1% of the delivered dose appeared in the ascites. Therefore, it is not plausible that the presence of ascites or other third spaces would have an impact on the pharmacokinetics of amifostine.