Pharmacokinetics, dose adjustments, and 6-mercaptopurine/ methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency

J. Brandt Andersen, C. Szumlanski, Richard M Weinshilboum, K. Schmiegelow

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Abstract

Two children with acute lymphoblastic leukaemia (ALL) were found to be thiopurine methyltransferase (TPMT)-deficient by both genotype and phenotype. They were monitored with haematological parameters and red blood cell concentrations of 6-thioguanine nucleotides (E-6TGN) and methotrexate (E- MTX, including MTX polyglutamates), in relation to the doses of 6- mercaptopurine (6MP) and methotrexate (MTX), during their maintenance chemotherapy. Both patients developed severe pancytopenia at the standard protocol dose of 6MP. Even at 25% and 5%, respectively, of the protocol dose of 6MP, they achieved E-6TGN values several-fold above the population median, but without unacceptable bone-marrow toxicity. Their high E-6TGN values had only a minor influence on their E-MTX values and their tolerance to oral MTX, but severe pancytopenia followed high-dose MTX infusions. Due to the risk of fatal myelosuppression we recommend up-front determination of TPMT activity in patients treated with 6MP or azathioprine.

Original languageEnglish (US)
Pages (from-to)108-111
Number of pages4
JournalActa Paediatrica, International Journal of Paediatrics
Volume87
Issue number1
DOIs
StatePublished - 1998

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6-Mercaptopurine
Drug Interactions
Methotrexate
Pharmacokinetics
thiopurine methyltransferase
Pancytopenia
Maintenance Chemotherapy
Azathioprine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Thiopurine S methyltranferase deficiency
Erythrocytes
Bone Marrow
Genotype
Phenotype
Population

Keywords

  • 6-mercaptopurine
  • Acute lymphoblastic leukaemia
  • Methotrexate
  • Thiopurine methyltransferase deficiency

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

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title = "Pharmacokinetics, dose adjustments, and 6-mercaptopurine/ methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency",
abstract = "Two children with acute lymphoblastic leukaemia (ALL) were found to be thiopurine methyltransferase (TPMT)-deficient by both genotype and phenotype. They were monitored with haematological parameters and red blood cell concentrations of 6-thioguanine nucleotides (E-6TGN) and methotrexate (E- MTX, including MTX polyglutamates), in relation to the doses of 6- mercaptopurine (6MP) and methotrexate (MTX), during their maintenance chemotherapy. Both patients developed severe pancytopenia at the standard protocol dose of 6MP. Even at 25{\%} and 5{\%}, respectively, of the protocol dose of 6MP, they achieved E-6TGN values several-fold above the population median, but without unacceptable bone-marrow toxicity. Their high E-6TGN values had only a minor influence on their E-MTX values and their tolerance to oral MTX, but severe pancytopenia followed high-dose MTX infusions. Due to the risk of fatal myelosuppression we recommend up-front determination of TPMT activity in patients treated with 6MP or azathioprine.",
keywords = "6-mercaptopurine, Acute lymphoblastic leukaemia, Methotrexate, Thiopurine methyltransferase deficiency",
author = "{Brandt Andersen}, J. and C. Szumlanski and Weinshilboum, {Richard M} and K. Schmiegelow",
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