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.

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 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: K R Herrlinger, K Fellermann, C Fischer, W Kreisel, P Deibert, J Schoelmerich, W E Fleig, A Ruhl, M Reinshagen, R Greinwald, E F Stange, M Schwab
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 19 Issue 12 Pg. 1269-76 (Jun 15 2004) ISSN: 0269-2813 [Print] England
• PMID: 15191508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Guanine Nucleotides
• Thionucleotides
• 6-thioguanylic acid
• Thioguanine

Topics

• Adult
• Biomarkers (blood)
• Crohn Disease (blood, drug therapy)
• Drug Monitoring (methods)
• Erythrocytes (metabolism)
• Female
• Guanine Nucleotides (blood)
• Humans
• Male
• Methylation
• Middle Aged
• Remission Induction
• Thioguanine (adverse effects, blood, therapeutic use)
• Thionucleotides (blood)
• Treatment Outcome