title: Monitoring of thiopurine methyltransferase activity in postsurgical patients with Crohn's disease during 1 year of treatment with azathioprine or mesalazine.
abstract: Thiopurine methyltransferase (TPMT) activity determines biotransformation of azathioprine and, thereby, drug efficacy and safety. Evaluation of a possible long-term effect of mesalazine or azathioprine on TPMT activity is of particular clinical importance because both drugs can to be given for several years in inflammatory bowel disease. Monitoring of TPMT activity and three thiopurine metabolites was performed prospectively during a 1 year postoperative period in 21 patients with Crohn's disease randomly assigned to azathioprine (2.0-2.5 mg/kg per day) or mesalazine (4 g/day). TPMT activity did not change significantly within each treatment group during 52 weeks. At any study visit, TPMT activity was not different between 13 patients on azathioprine and eight patients on mesalazine. Concentrations of 6-thioguanine nucleotides (6-TGN, active moiety of azathioprine) and 6-methyl-mercaptopurine ribonucleotides (6-MMPR) did not alter significantly during the observation period, except for a slight decrease in 6-TGN levels when comparing the first with the last visit. In this first report of serial monitoring of 6-methyl-thioguanine nucleotides (6-MTGN) in patients with inflammatory bowel disease taking azathioprine, high levels of 6-TGN were correlated with high levels of 6-MTGN, with the mean 6-TGN:6-MTGN ratio being 2.4. In a well-standardized clinical setting of inflammatory bowel disease, neither mesalazine nor azathioprine significantly affected TPMT activity during a whole year of treatment.
authors.affiliation: Dr Falk Pharma GmbH, Freiburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Dilger
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: Milan
authors.initials: M
authors.lastname: Lukas
authors.forename: Ulrike
authors.initials: U
authors.lastname: Strauch
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D001379:Azathioprine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006150:Guanine Nucleotides / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives / Q000378:metabolism; D019804:Mesalamine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D011184:Postoperative Period; D011446:Prospective Studies; D013866:Thioguanine / Q000031:analogs & derivatives / Q000378:metabolism; D013873:Thionucleotides / Q000378:metabolism; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D019804:Mesalamine; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine