伊立替康（CPT-11）及其代谢产物SN-38在人血液中的体外结合与分配
In vitro binding and partitioning of irinotecan (CPT-11) and its metabolite, SN-38, in human blood.
作者信息
Combes O, Barré J, Duché J C, Vernillet L, Archimbaud Y, Marietta M P, Tillement J P, Urien S
机构信息
Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, France.
出版信息
Invest New Drugs. 2000 Feb;18(1):1-5. doi: 10.1023/a:1006379730137.
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).
在37℃和pH 7.4条件下，通过超滤研究了CPT-11和SN-38与人血浆蛋白的结合情况。在血浆中，CPT-11在100 - 4000 ng/ml范围内的结合率为66% - 60%，SN-38在50 - 200 ng/ml范围内的结合率为94% - 96%。在这些浓度下，CPT-11的血浆结合略有饱和性，但SN-38的血浆结合与浓度无关。白蛋白是血浆中CPT-11和SN-38的主要载体。在血液中，CPT-11的结合率适中（80%），主要与血浆蛋白（47%）和红细胞（33%）结合。SN-38的结合率较高（99%），血液中大部分SN-38位于血细胞中（约66%）。对SN-38血液分布进行3级血液毒性模拟（根据美国国立癌症研究所的常见毒性标准分级），结果显示fu（血浆中药物的游离分数）从1.05增加到2.08，C(Bl)/C(P)从1.66降低到1.14（两者均因细胞结合减少所致）。
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