Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism

Nanne K.H. De Boer, Dennis R. Wong, Bindia Jharap, Peer De Graaf, Piet M. Hooymans, Chris J.J. Mulder, Frank Rijmen, Leopold G.J.B. Engels, Adriaan A. Van Bodegraven

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INTRODUCTION: Studies indicated that 5-aminosalicylates (5-ASA) may influence the metabolism of thiopurines; however, conclusions were restricted as a result of number of patients or study design. AIM: To determine the influence of 5-ASA on thiopurine metabolism, we performed a prospective multicenter pharmacokinetic interaction study of two different 5-ASA dosages (2 g daily followed by 4 g daily) in 26 inflammatory bowel disease (IBD) patients during steady-state AZA or 6-MP therapy. RESULTS: The 4-wk coadministration of 2 g 5-ASA daily, followed by a 4-wk period of 4 g 5-ASA daily, led to a statistical significant increase of 40% (absolute 84 pmol/8 × 108 RBC) and 70% (absolute 154 pmol/8 × 108 RBC) in 6-thioguaninenucleotide levels (6-TGN), respectively. A rise in 6-TGN levels was observed in 100% of patients after a 4-wk period of 4 g 5-ASA daily. The 6-methylmercaptopurine- ribonucleotide levels did not change. Signs of myelotoxicity were observed in 7.7% of patients (N = 2). CONCLUSIONS: The level of the pharmacologically active 6-TGN significantly increases in a dose-dependent manner during 5-ASA coadministration. IBD patients who are unresponsive or refractory to standard thiopurine therapy may benefit from the coadministration of 5-ASA, leading to an increase in 6-TGN levels.

Original languageEnglish
Pages (from-to)2747-2753
Number of pages7
JournalAmerican journal of gastroenterology
Issue number12
Publication statusPublished - 1 Dec 2007

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