期刊
GUT
卷 49, 期 5, 页码 656-664出版社
BRITISH MED JOURNAL PUBL GROUP
DOI: 10.1136/gut.49.5.656
关键词
azathioprine; 6-mercaptopurine; inflammatory bowel disease; leucopenia; mesalamine; sulphasalazine; balsalazide
资金
- NIDDK NIH HHS [DK 07198-22] Funding Source: Medline
- NIGMS NIH HHS [GM35720, GM28157] Funding Source: Medline
- FDA HHS [FD-T-000-886] Funding Source: Medline
Aim-We evaluated the effect of coadministration. of sulphasalazine, mesalamine, and balsalazide on the pharmacokinetics and pharmacodynamics of azathioprine and 6-mercaptopurine. Methods-Thirty four patients with Crohn's disease receiving azathioprine or 6-mercaptopurine were enrolled in an eight week non-randomised parallel group drug interaction study and treated with mesalamine 4 g/day, sulphasalazine 4 g/day, or balsalazide 6.75 g/day. The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined separately as total leucocyte counts < 3.0 x 10(9)/l and less than or equal to 3.5 x 10(9)/l. Whole blood 6-thioguanine nucleotide concentrations were determined. Results-Three patients could not be evaluated for the primary outcome measure. In the remaining 31. patients, the frequency of total leucocyte counts < 3.0 and 3.5 were: 1/10 and 5/10 in the mesalamine group; 1/11 and 6/11 in the sulphasalazine group; and 0/10 and 2/10 in the balsalazide group. There were significant increases mi mean whole blood 6-thioguanine nucleotide concentrations from baseline at most time points, in the mesalamine and sulphasalazine groups but not in the balsalazide group. Conclusions-In patients with Crohn's disease receiving azathioprine or 6-mercaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide results in an increase in whole blood 6-thinguanine, nucleotide, concentrations and a high frequency of leucopenia.
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