CELLULAR PHARMACOLOGY OF 6-MERCAPTOPURINE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

被引:0
作者
BOSTROM, B
ERDMANN, G
机构
[1] MINNEAPOLIS CHILDRENS HLTH CTR,DIV PEDIAT HEMATOL & ONCOL,MINNEAPOLIS,MN
[2] CHILDRENS CANC GRP,ARCADIA,CA
[3] N DAKOTA STATE UNIV,COLL PHARM,STATE TOXICOL LAB,FARGO,ND 58105
来源
AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY | 1993年 / 15卷 / 01期
关键词
6-MERCAPTOPURINE; ACUTE LYMPHOBLASTIC LEUKEMIA; CYTOTOXIC ACTIVITY; PHARMACOKINETICS;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:80 / 86
页数:7
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