title: Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease.
abstract: BACKGROUND
  6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine.
  
  
  OBJECTIVE
  To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease.
  
  
  METHODS
  6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity.
  
  
  RESULTS
  6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 x 10(8) red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels.
  
  
  CONCLUSIONS
  6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany. klaus.herrlinger@rbk.de
authors.forename: K R
authors.initials: KR
authors.lastname: Herrlinger
authors.forename: K
authors.initials: K
authors.lastname: Fellermann
authors.forename: C
authors.initials: C
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Kreisel
authors.forename: P
authors.initials: P
authors.lastname: Deibert
authors.forename: J
authors.initials: J
authors.lastname: Schoelmerich
authors.forename: W E
authors.initials: WE
authors.lastname: Fleig
authors.forename: A
authors.initials: A
authors.lastname: Ruhl
authors.forename: M
authors.initials: M
authors.lastname: Reinshagen
authors.forename: R
authors.initials: R
authors.lastname: Greinwald
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
authors.forename: M
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy*; D016903:Drug Monitoring / Q000379:methods; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D012074:Remission Induction; D013866:Thioguanine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013873:Thionucleotides / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; D013866:Thioguanine