Prospectief multicentrisch farmacokinetisch onderzoek: Invloed van mesalazine op het thiopurinemetabolisme bij patiënten met inflammatoire darmziekten

Translated title of the contribution: Influence of mesalazine on thiopurine metabolism in inflammatory bowel disease patients. Prospective multicenter pharmacokinetic study

D. R. Wong, N. K.H. De Boer, B. Jharap, P. De Graaf, A. A. Van Bodegraven, C. J.J. Mulder, L. G.J.B. Engels, P. M. Hooymans

Research output: Contribution to journalArticleProfessional

Abstract

Objective: To determine the influence of mesalazine (5-ASA) on thiopurine metabolism in inflammatory bowel disease (IBD) patients. Design: A prospective multicenter pharmacokinetic study of two different mesalazine dosages was performed in IBD patients using azathioprine (AZA) or mercaptopurine (6-MP). Methods: IBD patients on stable maintenance therapy (AZA or 6-MP for at least 8 weeks) with normal laboratory parameters were included in our study. Patients received consecutively per protocol two different dosages of mesalazine (2 g/day and 4 g/day). Laboratory parameters and levels of 6-thioguanine nucleotides (6-TGN), N-methylmercaptopurine ribonucleotides (6-MMPR), 5-ASA and N-acetyl-5-mesalazine (N-Ac-5-ASA) were determined before initiation and after 4, 8, 12 weeks. Adverse events were recorded. Results: 26 IBD patients were included. 4 weeks use of 2 g/day mesalazine, followed by a 4 week period of 4 g/day mesalazine, led to statistically significant increases (40% and 70%, respectively) in the mean 6-TGN levels. The rise of the active 6-TGN metabolite levels correlated with the mesalazine dosage, but not with mesalazine and N-Ac-5-ASA serum levels. 6-TGN levels significantly increased in a mesalazine dose-dependent manner; mesalazine had no significant influence on the hepatotoxic 6-MMPR metabolite levels during the entire study. 2 patients developed a temporary leucopenia. Conclusion: IBD patients who are unresponsive or refractory to standard thiopurine therapy, may benefit from the co-administration of mesalazine, due to an increase in 6-TGN metabolites.

Translated title of the contributionInfluence of mesalazine on thiopurine metabolism in inflammatory bowel disease patients. Prospective multicenter pharmacokinetic study
Original languageDutch
Pages (from-to)62-65
Number of pages4
JournalPharmaceutisch Weekblad
Volume143
Issue number12
Publication statusPublished - 21 Mar 2008

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