Portal de Periódicos da CAPES

Allopurinol safely and effectively optimizes tioguanine metabolites in inflammatory bowel disease patients not responding to azathioprine and mercaptopurine

2005; Wiley; Volume: 22; Issue: 5 Linguagem: Inglês

10.1111/j.1365-2036.2005.02583.x

1365-2036

Miles Sparrow, Scott A. Hande, Sonia Friedman, Wee Chian Lim, Sarathchandra I. Reddy, Dingcai Cao, Stephen B. Hanauer,

Pregnancy and Medication Impact

Summary Background : Many non‐responders to azathioprine or mercaptopurine (6‐mercaptopurine) have high normal thiopurine methyltransferase activity and preferentially metabolize mercaptopurine to produce 6‐methylmercaptopurine instead of the active 6‐tioguanine (6‐tioguanine) metabolites. Aim : To describe the use of allopurinol in mercaptopurine/azathioprine non‐responders to deliberately shunt metabolism of mercaptopurine towards 6‐tioguanine. Methods : Fifteen thiopurine non‐responders whose metabolites demonstrated preferential metabolism towards 6‐methylmercaptopurine are described. Subjects were commenced on allopurinol 100 mg po daily and mercaptopurine/azathioprine was reduced to 25–50% of the original dose. Patients were followed clinically and with serial 6‐tioguanine and 6‐methylmercaptopurine metabolite measurements. Results : After initiating allopurinol, 6‐tioguanine levels increased from a mean of 185.73 ± 17.7 to 385.4 ± 41.5 pmol/8 × 10 8 red blood cells ( P < 0.001), while 6‐methylmercaptopurine decreased from a mean of 10 380 ± 1245 to 1732 ± 502 pmol/8 × 10 8 RBCs ( P < 0.001). Allopurinol led to a decrease in white blood cell from a mean of 8.28 ± 0.95 to 6.1 ± 0.82 × 10 8 /L ( P = 0.01). Conclusions : 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.