Personalization of 6-mercaptopurine therapy — is diet the missing link?

Mercaptopurine (6-MP, 6-mercaptopurine) is an antineoplastic and immunosuppressive drug used, among others, in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This drug is a prodrug that is converted in the small intestine and liver into active metabolites, namely 6-thioguanine nucleotides (TGN), which exert cytotoxic effects. There are also pathways dependent on xanthine oxidase (XO) and thiopurine S-methyltransferase, leading to the formation of inactive metabolites. Studies on the influence of food on pharmacokinetic parameters indicate a reduction in the drug’s bioavailability. However, special attention should be paid to the interaction of this drug with dairy products, especially fresh cow’s milk, which has high enzymatic activity due to the natural presence of XO that can convert the drug into pharmacologically inactive 6-thiouric acid. Xanthine oxidase activity, however, decreases as a result of milk processing. In the case of human breast milk, XO activity is very low, which potentially indicates its minimal impact on the effectiveness of 6-MP therapy. Studies conducted in pediatric patients with ALL suggest that administering 6-MP with food or dairy products does not change TGN levels. In practice, this means that there is no need to introduce dietary restrictions in patients, which may facilitate better com-pliance, especially in children, due to the unpleasant taste of the preparation and the possibility of modifying it with dairy products. Similar mechanisms may apply to azathioprine and thioguanine, although there is a lack of direct clinical studies confirming this phenomenon.