Mercaptopurine (6-MP) and Thioguanine (6-TG) pharma

Mercaptopurine and thioguanine have low oral bioavailability because of first-pass metabolism by hepatic enzymes. The metabolism of 6-MP by xanthine oxidase is inhibited by the xanthine oxidase inhibitors allopurinol and febuxostat. Absorption by the oral route is erratic and incomplete. Once it enters the blood circulation, the drug is widely distributed throughout the body, except for the cerebrospinal fluid. The bioavailability of 6-MP can be reduced by the first-pass metabolism in the liver. While undergoing metabolism in the liver, 6-MP is converted to the 6-methylmercaptopurine derivative or to thiouric acid (an inactive metabolite). [Note: The latter reaction is catalyzed by xanthine oxidase.5] Because the xanthine oxidase inhibitor, allopurinol, is frequently used to reduce hyperuricemia in cancer patients receiving chemotherapy, it is important to decrease the dose of 6-MP by 75 percent in these individuals to avoid accumulation of the drug and exacerbation of toxicities. The parent drug and its metabolites are excreted by the kidney.