Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy

Content Provider	Scilit
Author	Graaf, P. De de Boer, Nanne Karner, S. Jharap, B. Hooymans, Pm Veldkamp, Ai Mulder, Cjj Bodegraven, Aa Van Schwab, M. Wong
Copyright Year	2010
Description	Journal: British Journal of Pharmacology 5-aminosalicylate (5-ASA) raises levels of 6-thioguanine nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN - 6-thioguanosine mono-, di- and triphosphate (6-TGMP, 6-TGDP, 6-TGTP) - and of 6-methylmercaptopurine ribonucleotides (6-MMPR) after 5-ASA are not known. Effects of increasing 5-ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4-week study periods. Patients started with 2 g 5-ASA daily, and then were increased to 4 g daily and followed by a washout period. Thiopurine doses remained unchanged throughout the entire study. Levels of 6-TGMP, 6-TGDP, 6-TGTP and 6-MMPR as well as of 5-ASA and N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) were determined each study period. Median baseline levels in 17 patients of 6-TGDP, 6-TGTP and 6-MMPR were 52, 319 and 1676 pmol per 8 x 10(8) red blood cells respectively. After co-administration of 2 g 5-ASA daily, median 6-TGDP and 6-TGTP levels increased but median 6-MMPR levels were unchanged. Increasing 5-ASA to 4 g daily did not affect median 6-TGDP and 6-TGTP levels, but median 6-MMPR levels decreased. After discontinuation of 5-ASA, both 6-TGDP and 6-TGTP levels decreased and median 6-MMPR levels increased. The 6-TGTP/(6-TGDP+6-TGTP)-ratio did not change during the study, but 6-MMPR/6-TGN ratios decreased. Individual 6-TGN metabolites increased after addition of 5-ASA, but 6-MMPR-levels and the 6-MMPR/6-TGN ratios decreased. Further studies are needed to decide whether this pharmacokinetic interaction would result in improvement of efficacy and/or increased risk of toxicity of AZA.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936018/pdf
Ending Page	1091
Starting Page	1083
ISSN	2573508X
e-ISSN	14765381
DOI	10.1111/j.1476-5381.2010.00731.x
Journal	British Journal of Pharmacology
Issue Number	5
Volume Number	160
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2010-03-05
Access Restriction	Open
Subject Keyword	Journal: British Journal of Pharmacology Medical Laboratory Technology 5‐aminosalicylates Inflammatory Bowel Disease 6‐thioguanine Nucleotides 6‐methyl‐mercaptopurine Ribonucleotides 6‐thioguanosine Triphosphate Clinical Pharmacology
Content Type	Text
Resource Type	Article