Abstract:
BACKGROUND:In vitro studies suggest interactions between mesalazine (mesalamine) and thiopurines by thiopurine S-methyltransferase (TPMT) inhibition, influencing the balance of hepatotoxic 6-methylmercaptopurine ribonucleotide and immunosuppressive tioguanine (thioguanine) metabolites. AIM:To examine the in vivo pharmacokinetic interaction between mesalazine and mercaptopurine. METHODS:A prospective study was performed in quiescent inflammatory bowel disease patients using the combination of mercaptopurine and mesalazine. Laboratory parameters, 6-methylmercaptopurine ribonucleotide and tioguanine levels and thiopurine S-methyltransferase activity in erythrocytes were measured at stable medication, after mesalazine discontinuation and mesalazine reintroduction, further mercaptopurine was continued. RESULTS:Seventeen patients were participated. Mean mercaptopurine dose was 0.78 mg/kg/day and median of mesalazine dose was 3000 mg/day. After mesalazine discontinuation, mean tioguanine levels changed significantly from 262 to 209 pmol/8 x 10(8) red blood cell, increasing to 270 after reintroduction. Mean 6-methylmercaptopurine ribonucleotide levels were 1422, 2149 and 1503 pmol/8 x 10(8) red blood cell respectively. Mean 6-methylmercaptopurine ribonucleotide/tioguanine ratio increased significantly from 6.3 at baseline to 11.2. Mean baseline thiopurine S-methyltransferase activity was 0.58 pmol/10(6) red blood cell/h and stable. All patients had wild-type thiopurine S-methyltransferase genotypes however, leucocyte counts were stable. DISCUSSION:A significantly higher tioguanine levels and improving 6-methylmercaptopurine ribonucleotide/tioguanine ratio were found during mesalazine/mercaptopurine combination. Theoretically, mesalazine inhibits thiopurine S-methyltransferase activity. In vivo thiopurine S-methyltransferase activity did not change, however. CONCLUSION:Mesalazine has synergistic effects on mercaptopurine therapy, but the mechanism is unclear. Combining these drugs may be further indication for mesalazine in inflammatory bowel disease treatment.
journal_name
Aliment Pharmacol Therjournal_title
Alimentary pharmacology & therapeuticsauthors
Gilissen LP,Bierau J,Derijks LJ,Bos LP,Hooymans PM,van Gennip A,Stockbrügger RW,Engels LGdoi
10.1111/j.1365-2036.2005.02630.xsubject
Has Abstractpub_date
2005-10-01 00:00:00pages
605-11issue
7eissn
0269-2813issn
1365-2036pii
APT2630journal_volume
22pub_type
临床试验,杂志文章abstract:BACKGROUND:Population data supporting an association between the autoimmune cholestatic liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis and coeliac disease, is limited and at times contradictory. AIM:To explore the relationship between coeliac disease and both primary biliary cirrhosis and...
journal_title:Alimentary pharmacology & therapeutics
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journal_title:Alimentary pharmacology & therapeutics
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pub_type: 杂志文章,多中心研究,随机对照试验
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Alimentary pharmacology & therapeutics
pub_type: 杂志文章
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更新日期:1993-06-01 00:00:00
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