Many non-responders to azathioprine or mercaptopurine have high normal thiopurine methyltransferase activity.
Som non-responders preferentially metabolize mercaptopurine to produce 6-methylmercaptopurine instead of the active 6-tioguanine metabolites.
Dr Sparrow and colleagues from Chicago described the use of allopurinol in mercaptopurine/azathioprine non-responders.
The research team deliberately shunted metabolism of mercaptopurine towards 6-tioguanine.
The researchers described 15 thiopurine non-responders whose metabolites demonstrated preferential metabolism towards 6-methylmercaptopurine.
| 6-tioguanine levels increased from a mean of 186 to 385 pmol/8 x108 red blood cells|
|Alimentary Pharmacology & Therapeutics|
Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to 25% to 50% of the original dose.
The team followed up patients clinically with serial 6-tioguanine and 6-methylmercaptopurine metabolite measurements.
After initiating allopurinol, the researchers found that 6-tioguanine levels increased from a mean of 186 to 385 pmol/8 x108 red blood cells.
The team noted that 6-methylmercaptopurine decreased from a mean of 10,380 ± to 1732 pmol/8 x 108 red blood cells.
Allopurinol led to a decrease in white blood cell from a mean of 8 to 6 x 108/L.
Dr Sparrow's team concluded, “The addition of allopurinol to thiopurine non-responders with preferential shunting to 6-methylmercaptopurine metabolites appears to be an effective means to shift metabolism towards 6-tioguanine.”