Authors: LENNARD, L.¹; WELCH, J.²; LILLEYMAN, J. S.¹

Source: British Journal of Clinical Pharmacology, Volume 42, Number 4, October 1996 , pp. 525-527(3)

Publisher: Wiley-Blackwell

Abstract:

The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75 mg/m² MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children (n=21) who tolerated 100% dosages and who were matched in this respect with a similar group of UKALL X children. Red blood cell MP derived thioguanine nucleotide (TGN) concentrations were measured in both groups under comparable conditions; at 75 mg/m² MP there was no significant difference. MP dose escalation in the UKALL XI children produced higher TGN concentrations (TGNs at 100%vs 125% dosages, median difference 90 pmol/8×10⁸ RBCs, 95% CI 25 to 165 pmol, P<0.02). Assayed at the time of cytopenia induced dose reduction, the UKALL XI children had accumulated significantly higher TGN concentrations than the UKALL X children (median difference 78 pmol/8×10⁸ RBCs, 95% CI 20 to 144, P<0.02). These findings indicate that dose escalation in children tolerant of 100% MP dosages produces higher peak TGN concentrations.

Keywords: childhood leukaemia; thioguanine nucleotides; mercaptopurine; compliance

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1365-2125.1996.44921.x

Affiliations: 1: University of Sheffield Department of Medicine and Pharmacology, Section of Molecular Pharmacology and Pharmacogenetics, The Royal Hallamshire Hospital, Sheffield S10 2JF, 2: University of Sheffield, Department of Paediatrics, Section of Paediatric Haematology, The Children's Hospital Sheffield, S10 2TH and Department of Paediatric Oncology, St Bartholomew's and the Royal London Hospital School of Medicine, St Barthol

Publication date: 1996-10-01

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