Authors: Herrlinger, K. R.¹; Fellermann, K.¹; Fischer, C.²; kreisel, W.³; Deibert, P.³; Schoelmerich, J.⁴; Fleig, W. E.⁵; Ruhl, A.⁶; Reinshagen, M.⁷; Greinwald, R.⁸; Stange, E. F.¹; Schwab, M.²

Source: Alimentary Pharmacology & Therapeutics, Volume 19, Number 12, June 2004 , pp. 1269-1276(8)

Publisher: Wiley-Blackwell

Abstract:

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 × 10⁸ red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 × 10⁸ 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.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2036.2004.01947.x

Affiliations: 1: Department of Gastroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany 2: Dr Margarete-Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany 3: Department of Internal Medicine II, Albert-Ludwigs-University, Freiburg, Germany 4: Department of Internal Medicine, University of Regensburg, Germany 5: 1st Department of Medicine, Martin-Luther-University, Halle, Germany 6: Department of Gastroenterology, Karl-Ruprechts-University, Heidelberg, Germany 7: Department of Medicine I, Albert-Einstein-University, Ulm, Germany 8: Dr Falk-Pharma GmbH, Freiburg, Germany

Publication date: 2004-06-01

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• In this Subject: Pathology ,  Pharmacology ,  Surgery ,  Therapeutics & Alternative Medicine
• By this author: 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.

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