HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsJ B Andersen, C Szumlanski, R M Weinshilboum, K Schmiegelow
JournalActa paediatrica (Oslo, Norway : 1992) (Acta Paediatr) Vol. 87 Issue 1 Pg. 108-11 (Jan 1998) ISSN: 0803-5253 [Print] Norway
PMID9510461 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Mercaptopurine
  • Methyltransferases
  • thiopurine methyltransferase
  • Methotrexate
Topics
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacokinetics)
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Follow-Up Studies
  • Humans
  • Male
  • Mercaptopurine (administration & dosage)
  • Methotrexate (administration & dosage)
  • Methyltransferases (deficiency)
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (complications, diagnosis, drug therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: