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Variability of 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute leukemia

  • Pierre Lafolie
  • Olle Björk
  • Salah Hayder
  • Lars Åhström
  • Curt Peterson
Original Articles
  • 82 Downloads

Abstract

The effects of some environmental and genetic factors on the inter- and intraindividual variations of 6-mercaptopurine (6-MP) pharmacokinetics were studied in children on oral remission maintenance therapy for acute lymphoblastic leukemia or non-Hodgkin’s lymphoma. Blood samples were obtained 0–4 h after drug intake. 6-MP concentrations were determined in plasma and in erythrocyte concentrates. The influence of food on the pharmacokinetics was examined in a prospective study of 15 children. Each child was examined four times, twice in the fasted state and twice after intake of a standardized, milky, breakfast. There were pronounced inter- and intraindividual variations. Food intake seemed to reduce these variations but there were no significant changes in peak concentrations and area under the plasma concentration vs time curves (AUC) between the fasted and fed states. Food intake reduced the time to peak concentration both in plasma, from 1.8 h to 1.1 h (P < 0.01) and in red blood cells, from 1.8 h to 1.3 h (P < 0.01). Retrospective subdivision of the patients indicated a tendency for different pharmacokinetic patterns according to dose; five out of seven patients receiving > 70 mg m−2 had a higher AUC in the fasting state, while five out of eight patients receiving <70 mg m−2 had a higher AUC in the fed state. The cytochrome P-450-dependent hydroxylation capacity was evaluated with debrisoquine but no correlation was found to the pharmacokinetics of 6-MP.

Key words

6-Mercaptopurine Pharmacokinetics Leukemia Variability Children 

Abbreviatións used in this paper

6-MP

6-mercaptopurine

ALL

acute lymphoblastic leukemia

NHL

non-Hodgkin’s lymphoma

AUC

area under the concentration vs time curve

HPLC

high-performance liquid chromatography

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Copyright information

© Humana Press Inc. 1989

Authors and Affiliations

  • Pierre Lafolie
    • 1
  • Olle Björk
    • 2
  • Salah Hayder
    • 2
  • Lars Åhström
    • 2
  • Curt Peterson
    • 1
  1. 1.Department of Clinical PharmacologyKarolinska HospitalStockholmSweden
  2. 2.Department of Pediatric OncologyKarolinska HospitalStockholmSweden

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