Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia.
Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia.
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DOI：
10.1097/00043426-199302000-00010
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发表时间：
1993-02
期刊：
影响因子：
--
通讯作者：
B. Bostrom;G. Erdmann
中科院分区：
文献类型：
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作者：
B. Bostrom;G. Erdmann
目的综述6-巯基嘌呤（6-Mercaptopurine，6 MP）治疗急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）的细胞药理学研究进展。设计：对6 MP临床药理学的相关研究进行综述。结果6 MP是急性淋巴细胞白血病（ALL）维持治疗的主要药物之一。它也用于治疗类固醇无反应的炎症性肠病。6 MP是一种无活性的前药，需要吸收、细胞摄取和细胞内与核苷酸结合以获得细胞毒性活性。这些核苷酸最终被整合到DNA和RNA中，导致细胞死亡。6 MP的两种类似物硫唑嘌呤和6-硫鸟嘌呤也被合成代谢为相同的细胞内代谢物，这表明它们在治疗上应该与6 MP等效。6 MP可以被合成代谢为非甲基化的核苷酸，或者可以通过硫嘌呤甲基转移酶甲基化为S-甲基化的核苷酸，这也是细胞毒性的。结论近期ALL患儿的6 MP药代动力学研究表明，较高的全身暴露量（如血药浓度-时间曲线下面积较大或红细胞中6 MP代谢产物浓度较高）与复发风险降低相关。
PURPOSE The cellular pharmacology of 6-Mercaptopurine (6MP) in acute lymphoblastic leukemia (ALL) is reviewed. DESIGN Relevant studies on the clinical pharmacology of 6MP were reviewed. RESULTS 6MP is one of the major drugs used in maintenance therapy of acute lymphoblastic leukemia (ALL). It is also used to treat steroid unresponsive inflammatory bowel disease. 6MP is an inactive prodrug that requires absorption, cellular uptake, and intracellular anabolism to nucleotides for cytotoxic activity. These nucleotides are ultimately incorporated into DNA and RNA, resulting in cell death. Two analogs of 6MP, azathioprine and 6-thioguanine, are also anabolized to the same intracellular metabolites, suggesting they should be therapeutically equivalent to 6MP. 6MP may be anabolized to nonmethylated nucleotides or may undergo methylation by the enzyme thiopurine methyltransferase to S-methylated nucleotides, which are also cytotoxic. CONCLUSION Recent studies of 6MP pharmacokinetics in children with ALL have suggested that a higher systemic exposure, as measured by a greater area under the plasma concentration time curve or a higher concentration of 6MP metabolites in red blood cells, is associated with a decreased risk of relapse.