PMID- 9225958 OWN - NLM STAT- MEDLINE DCOM- 19970807 LR - 20171116 IS - 0344-5704 (Print) IS - 0344-5704 (Linking) VI - 40 IP - 4 DP - 1997 TI - Methotrexate increases red blood cell concentrations of 6-methylmercaptopurine ribonucleotide in rats in vivo. PG - 367-70 AB - PURPOSE: 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. FAU - Giverhaug, T AU - Giverhaug T AD - Department of Pharmacology, University of Tromso, Norway. FAU - Fuskevaag, O M AU - Fuskevaag OM FAU - Aarbakke, J AU - Aarbakke J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Cancer Chemother Pharmacol JT - Cancer chemotherapy and pharmacology JID - 7806519 RN - 0 (Guanine Nucleotides) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (Thionucleotides) RN - 15867-02-4 (6-thioguanylic acid) RN - 342-69-8 (Methylthioinosine) RN - E7WED276I5 (Mercaptopurine) RN - EC 2.1.1.- (Methyltransferases) RN - EC 2.1.1.67 (thiopurine methyltransferase) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Animals MH - Erythrocytes/drug effects/*metabolism MH - Guanine Nucleotides/analysis/metabolism MH - Male MH - Mercaptopurine/*metabolism/pharmacology MH - Methotrexate/*pharmacology MH - Methylthioinosine/analysis/metabolism MH - Methyltransferases/metabolism MH - Nucleic Acid Synthesis Inhibitors/*pharmacology MH - Rats MH - Rats, Wistar MH - Thionucleotides/analysis/metabolism EDAT- 1997/01/01 00:00 MHDA- 1997/01/01 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1997/01/01 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] AID - 10.1007/s002800050672 [doi] PST - ppublish SO - Cancer Chemother Pharmacol. 1997;40(4):367-70. doi: 10.1007/s002800050672.