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Metabolism of Intravenously Administered High-Dose 6-Mercaptopurine with and without Allopurinol Treatment in Patients with Non-Hodgkin Lymphoma

1996; Lippincott Williams & Wilkins; Volume: 18; Issue: 2 Linguagem: Inglês

10.1097/00043426-199605000-00009

1536-3678

C.W. Keuzenkamp-Jansen, Ronney A. De Abreu, J.P.M. Bökkerink, M.A.H. Lambooy, J. M. F. Trijbels,

Pregnancy and Medication Impact

Purpose: We investigated the metabolism of high dose 6 mer-captopurine (HD-6MP) infusions and its influenee on the metabolism by allopurinol, an inhibitor of xanthinc oxidase, the enzyme that catabolizes 6MP into thioxanthine and thiourie acid. Patients and Methods: Nine patients (aged 2− 11 years) with non-Hodgkin lymphoma (NHL) were treated with HD-6MP (1300 mg/m2.24 h) within a therapeutic window after diagnosis. Four patients received oral allopurinol (200 mg/m2.day) to prevent urate nephropathy, and five did not. Plasma and RBC were isolated before and 4, 20, 24, 28, and 48 h after the start of the infusion. All measurements were performed with HPLC. Results: Considerable variations were found in the plasma levels of 6MP. thioxanthine. and thiourie acid and of RBC-MeTIN levels. 6MP-ribosidc was not detectable, and MeMP and MeMPR levels were <1.3 M in the plasma. In general, 6MP, thioxanthine, and McMP levels in plasma were higher, and thiourie acid plasma levels and RBC-MeTIN levels were lower in the patients treated with allopurinol compared to those who did not receive allopurinol. Conclusions: 6MP is extensively metabolized in patients with NHL treated with HD-6MP. Thiopurine mcthylation, at the levels of nuclcotide. nucleoside. and base, is an important metabolic pathway after HD-6MP. Co-administration of allopurinol can result in both a decreased catabolism and anabolism of 6MP compared to treatment with HD-6MP alone. This observation may have consequences for the therapeutic efficacy and toxic effects of 6MP in combination with allopurinol.