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News

Allopurinol optimises thiopurine metabolites in patients with autoimmune hepatitis

Allopurinol safely and effectively optimises thiopurine metabolites in patients with autoimmune hepatitis, reports the latest issue of the Alimentary Pharmacology & Therapeutics.

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About 10% of patients with autoimmune hepatitis are nonresponsive or intolerant to thiopurine therapy.

A skewed metabolism, leading to the preferential generation of toxic thiopurine metabolites instead of the metabolic active 6-tioguanine nucleotides, may explain this unfavorable outcome.

Dr de Boer and colleages examined co-administration of allopurinol to low-dose thiopurine therapy may effectively revert this deviant metabolism, as has been shown in inflammatory bowel disease.

The team described the effect of adding allopurinol to low-dose thiopurine therapy in patients with AIH with intolerance or nonresponse to normal thiopurine dosages due to a skewed metabolism.

The researchers examined the clinical efficacy and tolerability of allopurinol–thiopurine combination therapy with allopurinol 100 mg and low-dose thiopurine in eight AIH patients with a skewed thiopurine metabolism.

Patients were switched because of dose-limiting intolerance, nonresponse or loss of response to conventional thiopurine treatment.

All 8 patients showed biochemical improvement with a reduction
Alimentary Pharmacology & Therapeutics

The research team reported that all 8 patients showed biochemical improvement with a reduction in median alanine aminotransferase levels of 62 U/L at start to 35 U/L at 1 month.

This clinical benefit was sustained in 7 patients.

The doctors found that allopurinol–thiopurine combination therapy effectively bypassed thiopurine side effects in 4 of 5 patients.

Median 6-tioguanine nucleotides levels increased from 100 to 200 pmol/8 × 108 red blood cells at 3 months.

The researchers observed that median 6-MMP levels decreased in all patients from 6090 to 175 pmol/8 × 108 RBC.

Dr de Boer's team concluded, "Allopurinol safely and effectively optimises thiopurine therapy in patients with autoimmune hepatitis with intolerance and/or nonresponse due to an unfavorable thiopurine metabolism."

Aliment Pharmacol Ther 2013: DOI: 10.1111/apt.12223


08 February 2013

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