Publications by authors named "Jarle Aarbakke"

3 Publications

  • Page 1 of 1

[Strange reaction to drug therapy].

Tidsskr Nor Laegeforen 2003 Jun;123(13-14):1910

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June 2003

[Drug therapy].

Tidsskr Nor Laegeforen 2003 Feb;123(4):476-7

Farmakologisk avdeling Institutt for medisinsk biologi, Universitetet i Tromsø 9037 Tromsø.

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February 2003

[New techniques for optimization of thiopurine therapy in leukemia and transplantation].

Tidsskr Nor Laegeforen 2002 Apr;122(11):1107-10

Avdeling for farmakologi Institutt for farmasi, Universitetet i Tromsø 9037 Troms.

Background: The majority of chemotherapeutic agents are administered at fixed doses that are close to those maximally tolerated.

Material And Methods: This review is based on current knowledge about the metabolism of thiopurines and the clinical implications of genetic polymorphism in thiopurine-S-methyltransferase (TPMT).

Results: Intracellularly thiopurines, e.g. 6-MP, are anabolized to cytotoxic 6-thioguanine nucleotides (6-TGN) that are incorporated into DNA and RNA. A competing pathway is S-methylation of 6-MP and its initial nucleotide metabolites by TPMT. In childhood acute lymphocytic leukaemia, high erythrocyte concentrations of 6-TGN correlate with the degree of leukopenia and a good prognosis, while low concentrations appear to be associated with higher risk of relapse. In most populations studied, approximately 10% have intermediate TPMT activity and 1/300 lacks TPMT activity due to one or two mutant TPMT alleles, respectively.

Interpretation: Phenotyping or genotyping may be used to identify patients as deficient or intermediate thiopurine metabolizers. This suggests that they should receive a profound or moderate reduction in dosage to avoid haematopoietic toxicity.
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April 2002
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