A comparison of red blood cell thiopurine metabolites in children with acute lymphoblastic leukemia who received oral mercaptopurine twice daily or once daily: a Pediatric Oncology Group study (now The Children's Oncology Group)

Pediatric Blood & Cancer
B A BellPediatric Oncology Group study (now The Children's Oncology Group)

Abstract

Mercaptopurine is an important antimetabolite for treatment of childhood acute lymphoblastic leukemia (ALL). It has been prescribed to be given daily without therapeutic monitoring of drug levels. After first-pass metabolism by hepatic xanthine oxidase (XO), mercaptopurine is converted into two major intracellular metabolites, thioguanine nucleotide (TGN) and methylated mercaptopurine metabolites (including methylated thioinosine nucleotides), which are cytotoxic in vitro. Its short plasma half-life and S-phase-dependent pharmacokinetics suggest that biologically active concentration and exposure duration may be critical to cell kill. Pediatric Oncology Group (POG) 9605, a randomized, open label phase III study of standard-risk ALL, was designed to compare daily with twice-daily mercaptopurine during continuation therapy. Red blood cell (RBC) TGN and methylated mercaptopurine metabolite levels were measured as surrogates of leukemic cell levels in a randomly selected subset of patients. TGN and methylated mercaptopurine metabolites were analyzed quantitatively by high-performance liquid chromatography (HPLC) and reported in ng/8 x 10.8 RBC. Statistical inferences utilized multiple linear regression. One hundred eighteen patient...Continue Reading

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Citations

May 29, 2008·European Journal of Clinical Pharmacology·Srikumar SahasranamanSandip Roy
Mar 6, 2012·Journal of Crohn's & Colitis·Melissa A SmithJeremy D Sanderson
Apr 29, 2015·Expert Review of Gastroenterology & Hepatology·Rimma Goldberg, Peter M Irving
Jun 3, 2009·Pediatric Blood & Cancer·Jeong A ParkJong Jin Seo
Sep 11, 2007·Drug Metabolism and Pharmacokinetics·Mohammad-Reza RashidiSoodabeh Davaran
Aug 30, 2014·Journal of Pediatric Hematology/oncology·Stine N NielsenKjeld Schmiegelow
Oct 14, 2014·PloS One·Devaraj JayachandranDoraiswami Ramkrishna
Apr 15, 2011·Cancer Treatment Reviews·Hendrik van den BergJos H Beijnen
Jun 18, 2014·Journal of Pediatric Hematology/oncology·Kjeld SchmiegelowJacob Nersting
Aug 27, 2016·Clinical Pharmacology and Therapeutics·C LiuM V Relling

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