title: Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia.
abstract: OBJECTIVE
  The cellular pharmacology of 6-Mercaptopurine (6MP) in acute lymphoblastic leukemia (ALL) is reviewed.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Hematology and Oncology, Minneapolis Children's Medical Center, MN.
authors.forename: B
authors.initials: B
authors.lastname: Bostrom
authors.forename: G
authors.initials: G
authors.lastname: Erdmann
mesh_terms: D001682:Biological Availability; D001711:Biotransformation; D002648:Child; D002940:Circadian Rhythm; D004912:Erythrocytes / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D015122:Mercaptopurine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism*; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D009696:Nucleic Acids; D011355:Prodrugs; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase