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 24 May 2018

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Mesalazine combination therapy in IBD

Mesalazine has synergistic effects on mercaptopurine therapy, and combining these drugs may be further indication for mesalazine in inflammatory bowel disease treatment, shows October's Alimentary Pharmacology & Therapeutics.

News image

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In vitro studies suggest interactions between mesalazine and thiopurines by thiopurine S-methyltransferase inhibition.

These influence the balance of hepatotoxic 6-methylmercaptopurine ribonucleotide and immunosuppressive tioguanine metabolites.

Dr Gilissen and colleagues examined the in vivo pharmacokinetic interaction between mesalazine and mercaptopurine.

The researchers performed a prospective study in quiescent inflammatory bowel disease patients.

The research team used the combination of mercaptopurine and mesalazine.

Laboratory parameters, 6-methylmercaptopurine ribonucleotide and tioguanine levels were measured.

The team also measured thiopurine S-methyltransferase activity in erythrocyes at stable medication.

6-methylmercaptopurine ribonucleotide/tioguanine ratio increased from 6 to 11
Alimentary Pharmacology & Therapeutics

After mesalazine discontinuation and mesalazine reintroduction, further mercaptopurine was continued.

The team reported that 17 patients participated.

The mean mercaptopurine dose was 0.8 mg/kg/day and median of mesalazine dose was 3000 mg/day.

After mesalazine discontinuation, tioguanine levels changed from 262 to 209 pmol/8x108 red blood cell, increasing to 270 after reintroduction.

The researchers found that mean 6-methylmercaptopurine ribonucleotide levels were 1422, 2149 and 1503 pmol/8x108 red blood cell respectively.

Mean 6-methylmercaptopurine ribonucleotide/tioguanine ratio increased significantly from 6 at baseline to 11.

The team noted that mean baseline thiopurine S-methyltransferase activity was 0.6 pmol/106 red blood cell/h and stable.

The researchers found that all patients had wild-type thiopurine S-methyltransferase genotypes however, leucocyte counts were stable.

A higher tioguanine levels and improving 6-methylmercaptopurine ribonucleotide/tioguanine ratio were found during mesalazine/mercaptopurine combination.

Theoretically, mesalazine inhibits thiopurine S-methyltransferase activity.

However, the team observed that in vivo thiopurine S-methyltransferase activity did not change.

Dr Gilissen's team concludes, “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.”

Aliment Pharmacol Ther 2005: 22(7): 605
03 October 2005

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