In vitro binding and partitioning of irinotecan (CPT-11) and its metabolite, SN-38, in human blood
In vitro binding and partitioning of irinotecan (CPT-11) and its metabolite, SN-38, in human blood
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DOI：
10.1023/a:1006379730137
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发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Urien, S
中科院分区：
文献类型：
--
作者：
Combes, O;Barré, J;Urien, S
在37℃、pH 7.4的条件下，用超滤法研究了CPT-11和SN-38与人血浆蛋白的结合。在血浆中，CPT-11的结合率为66-60%，结合率为100-4000 ng/ml，SN-38的结合率为94-96%，结合率为50-200 ng/ml，在这些浓度下，CPT-11的血浆结合率略有饱和，而SN-38的结合率不受浓度的影响。白蛋白是CPT-11和SN-38在血浆中的主要载体。在血液中，CPT-11的结合率为中等(80%)，主要与血浆蛋白(47%)和红细胞(33%)结合。SN-38的结合率很高(99%)，血液中的SN-38大部分位于血细胞中(约66%)。对SN-38血液分布的模拟3级血液毒性(根据国家癌症研究所的共同毒性分级)产生的FU(血浆中药物的游离分数)从1.05增加到2.08，C-B1/C-P从1.66下降到1.14(两者都是由于细胞结合减少)。
The binding of CPT-11 and SN-38 to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. In plasma, CPT-11 was 66-60% bound in the range 100-4000 ng/ml and SN-38 was 94-96% bound in the range 50-200 ng/ml. At these concentrations the plasma binding of CPT-11 was slightly saturable, but the plasma binding of SN-38 was concentration-independent. Albumin was the main carrier of CPT-11 and SN-38 in plasma. In blood, the binding of CPT-11 was moderate (80%), mainly to plasma proteins (47%) and erythrocytes (33%). The binding of SN-38 was high (99%) and most of SN-38 in blood was located in blood cells (approximately 66%) The simulation of a grade 3 hematotoxicity (according to National Cancer Institute's Common Toxicity Criteria grading) on the SN-38 blood distribution yielded an increase in fu (free fraction of drug in plasma) from 1.05 to 2.08 and a decrease in C-Bl/C-P from 1.66 to 1.14 (both resulting from a decreased cell binding).