Pharmacokinetics of tablet and liquid formulations of oral 6-mercaptopurine in children with acute lymphoblastic leukemia

Cancer Chemother Pharmacol. 2020 Jul;86(1):25-32. doi: 10.1007/s00280-020-04097-x. Epub 2020 Jun 9.


Purpose: Mercaptopurine (6MP) is essential to cure childhood acute lymphoblastic leukemia (ALL). A liquid 6MP formulation was recently introduced to facilitate oral 6MP administration, especially to children. Its approval and bioequivalence with 6MP tablet were based on comparative pharmacokinetics in 60 healthy adults. Due to potential pharmacokinetic differences between healthy adults and children with ALL, we compared pharmacokinetics of tablet and liquid 6MP formulations in children with ALL.

Methods: Pharmacokinetics of 50 mg 6MP tablet (Puri-Nethol®) and 20 mg/ml 6MP liquid suspension (Xaluprine®) were compared in a non-blinded, random order, single-dose, cross-over study in 16 children with ALL (eight males). 6MP was administered after a 12 h fast, and 6MP plasma concentrations measured consecutively over seven hours post-dose. Pharmacokinetic outcomes were as follows: Area under the curve (AUC), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and terminal half-life (T½).

Results: Liquid 6MP formulation resulted in a 26% lower AUC (p = 0.02) compared with tablet (median 1215 vs. 1805 h × nmol/l). No significant differences were observed for Cmax,Tmax and T½ (p = 0.28, p = 0.09, p = 0.41, respectively). Based on criteria declared by the World Health Organization the results did not establish non-inferiority of liquid 6MP formulation compared with 6MP tablet.

Conclusion: Non-inferiority of liquid 6MP formulation compared with 6MP tablet was not demonstrated. Yet, maintenance therapy doses are adjusted by degree of myelosuppression and not by 6MP dose. Thus, in spite of a lower bioavailability, a liquid 6MP formulation is still desirable in a clinical setting, especially for children. However, if shifting between 6MP formulation is indicated, dose adjustments should be anticipated to maintain equivalent treatment intensity in children with ALL. The study is registered on (NCT01906671). Date of registration: 24.07.13.

Keywords: Cancer; Childhood acute lymphoblastic leukemia; Leukemia; Mercaptopurine; Pharmacokinetics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / blood
  • Antimetabolites, Antineoplastic / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Child
  • Child, Preschool
  • Cross-Over Studies
  • Female
  • Humans
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / blood
  • Mercaptopurine / pharmacokinetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Tablets / administration & dosage
  • Tablets / pharmacokinetics


  • Antimetabolites, Antineoplastic
  • Tablets
  • Mercaptopurine

Associated data