J Korean Pediatr Soc.  1994 Dec;37(12):1732-1737.

The Effect of Milk on the Bioavailability of 6-mercaptopurine

• Park SK
• Kim RJ
• Hwang PH
• Cho SC
• Kim JS

Abstract

The purine antimetabolite 6-Mercaptopurine (6-MP) has been in clinical use for over 30 years and is still a widely used agent in the treatment of childhood acute lymphoblastic leukemia. The bioavailibility, clinical efficacy and toxicity of 6-MP administered orally for maintenance therapy of children with acute lymphoblastic leukemia are highly variable in many studies, as well as at differnt times in same patient. there are many factors affecting the bioavailibility of 6-MP. The most notably factor being that concomitantly administered drugs and foods might contribute to a decrease in the bioavailibity of this drug. In our sociocultural environment milk is a major constituent of child's foods. Cow's milk contains a high concentration of xanthine oxidase, which could potentially transform 6-TM into 6-thioxanthine (6-TX) and 6-thiouric acid (6-TUA) which have no more therapeutic effects. In this study, we evaluated the effect of various milk products on the bioavailability of 6-MP. Incubation at 37degrees C for 30 min raw or pasteurized milk resulted in transformation of a large quantity of clinically relevant concentration of 6-MP into 6-TUA. The concomitant adminstration of folic acid and allopurinol has markedly inhibitory effect on the 6-MP destroying activity of milk at clinically relevant concentrations. These observations may help to optimize modalities of administration of 6-MP for the treartment of patients with childhood leukemia.

MeSH Terms

6-Mercaptopurine*
Allopurinol
Biological Availability*
Child
Complement Factor B
Folic Acid
Humans
Leukemia
Milk*
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Xanthine Oxidase
6-Mercaptopurine
Allopurinol
Complement Factor B
Folic Acid
Xanthine Oxidase