title: Methotrexate increases red blood cell concentrations of 6-methylmercaptopurine ribonucleotide in rats in vivo.
abstract: OBJECTIVE
  To elucidate the effect of methotrexate (MTX) on 6-mercaptopurine (6-MP) metabolism in rats.
  
  
  METHODS
  Fourteen rats were given 6-MP 20 mg/kg daily for 7 days. Seven of the rats were also given MTX 20 mg/kg on days 5 and 7. Blood samples were obtained from all rats on days 0.5 and 8, and red blood cell (RBC) lysates were analysed for thiopurine methyltransferase (TPMT) activity and the concentration of methylated 6-MP metabolites [methyl mercaptopurine ribonucleotides (MMPRP)] and 6-thioguanine nucleotides (6-TGN).
  
  
  RESULTS
  The concentration of MMPRP increased 2.4 times from day 5 to day 8 in RBCs from rats given MTX in addition to 6-MP, as against 1.2 times in rats given 6-MP alone (P = 0.003). 6-TGN levels increased and TPMT activity decreased from day 5 to day 8, with no difference between the 6-MP and the 6-MP plus MTX groups.
  
  
  CONCLUSIONS
  Single bolus doses of MTX increase the concentration of MMPRP in rats given daily s.c. doses of 6-MP, with no effect on 6-TGN concentration or TPMT activity.
authors.affiliation: Department of Pharmacology, University of Tromsø, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Giverhaug
authors.forename: O M
authors.initials: OM
authors.lastname: Fuskevaag
authors.forename: J
authors.initials: J
authors.lastname: Aarbakke
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000032:analysis / Q000378:metabolism; D008297:Male; D015122:Mercaptopurine / Q000378:metabolism* / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology*; D008778:Methylthioinosine / Q000032:analysis / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013873:Thionucleotides / Q000032:analysis / Q000378:metabolism
chemical_list: D006150:Guanine Nucleotides; D019384:Nucleic Acid Synthesis Inhibitors; D013873:Thionucleotides; C003964:6-thioguanylic acid; D008778:Methylthioinosine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D008727:Methotrexate