TY - JOUR
T1 - Dose-dependent influence of 5-aminosalicylates on thiopurine metabolism
AU - De Boer, Nanne K.H.
AU - Wong, Dennis R.
AU - Jharap, Bindia
AU - De Graaf, Peer
AU - Hooymans, Piet M.
AU - Mulder, Chris J.J.
AU - Rijmen, Frank
AU - Engels, Leopold G.J.B.
AU - Van Bodegraven, Adriaan A.
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=36549028729&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/j.1572-0241.2007.01511.x
DO - https://doi.org/10.1111/j.1572-0241.2007.01511.x
M3 - Article
C2 - 17764493
SN - 0002-9270
VL - 102
SP - 2747
EP - 2753
JO - American journal of gastroenterology
JF - American journal of gastroenterology
IS - 12
ER -