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Thioguanine‐nucleotides do not predict efficacy of tioguanine in Crohn's disease
Author(s) -
Herrlinger K. R.,
Fellermann K.,
Fischer C.,
Kreisel W.,
Deibert P.,
Schoelmerich J.,
Fleig W. E.,
Ruhl A.,
Reinshagen M.,
Greinwald R.,
Stange E. F.,
Schwab M.
Publication year - 2004
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2004.01947.x
Subject(s) - nucleotide , azathioprine , thiopurine methyltransferase , medicine , mercaptopurine , pharmacology , chemistry , disease , biochemistry , gene
Summary 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. Aim : 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 × 10 8 red blood cells (range 313–1853)]. Methylated 6‐thioguanine‐nucleotide levels were detected in all patients [491 pmol/8 × 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.