期刊
AMERICAN JOURNAL OF GASTROENTEROLOGY
卷 102, 期 12, 页码 2747-2753出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1572-0241.2007.01511.x
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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 x 10(8) RBC) and 70% (absolute 154 pmol/8 x 10(8) 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.
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