title: A novel 6-mercaptopurine oral liquid formulation for pediatric acute lymphoblastic leukemia patients - results of a randomized clinical trial.
abstract: OBJECTIVE
  Pediatric patients with acute lymphoblastic leukemia (ALL) are treated with oral 6-mercaptopurine (6MP) for nearly 2 years, but no pediatric formulation has been available. In this study, an oral 6MP liquid suitable for pediatric use was developed and tested in the target population.
  
  
  METHODS
  A randomized cross-over study was performed in 20 pediatric ALL patients (age 1.9 - 14.6 years), comparing pharmacokinetics and pharmacodynamics of a newly developed 6MP liquid formulation to 6MP capsules, both taken orally for 4 weeks.
  
  
  RESULTS
  Based upon trough levels of the principal active metabolite,6-thioguanine nucleotides (6-TGN),a relative bioavailability of the liquid vs. capsules of 1.01 was found (90% CI 0.86 - 1.20), demonstrating bioequivalence. This was supported by the similarly observed 6MP dosages needed for leucocyte depletion, for both formulations (35 mg/day (range 10 - 115 mg)). 75% of the parents/patients (p = 0.005) preferred the oral liquid over the capsules because of the ease of administration.
  
  
  CONCLUSIONS
  We conclude that the novel 6MP liquid is a promising treatment for ALL.
authors.forename: Lidwien M
authors.initials: LM
authors.lastname: Hanff
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathot
authors.forename: Oscar
authors.initials: O
authors.lastname: Smeets
authors.forename: Doerine J
authors.initials: DJ
authors.lastname: Postma
authors.forename: Satianand
authors.initials: S
authors.lastname: Ramnarain
authors.forename: Andras
authors.initials: A
authors.lastname: Vermes
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013810:Therapeutic Equivalency; D013873:Thionucleotides / Q000097:blood*; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D015122:Mercaptopurine