Milk could decrease the bioavailability of 6-mercaptopurine.
The bioavailability of 6-mercaptopurine (6-MP) administered orally for maintenance therapy of children with acute lymphoblastic leukemia is highly variable. Xanthine oxidase (XO) can transform 6-MP into 6-thioxanthine (6-TX) and 6-thiouric acid (6-TUA), which have no therapeutic value. XO is found in high concentration in cow's milk. Incubation at 37 degrees C for 30 min with commercial preparations of pasteurized cow's milk results in transformation of 30% of a clinically relevant concentration of 6-MP into 6-TUA. Milk boiled for 5 min has no effect on the 6-MP. Addition of gastric juice at ratios likely to be seen in children has negligible inhibitory effect on the 6-MP destroying activity of milk. Conversely, folic acid and allopurinol markedly inhibit this effect at clinically relevant concentrations. These observations may help to optimize modalities of administration of 6-MP.
Rivard
G E
GE
Centre de Recherche Pediatrique, Hôpital Sainte-Justine, Montréal, Québec, Canada.
Lin
K T
KT
Leclerc
J M
JM
David
M
M
D000818:Animals; D001682:Biological Availability; D015122:Mercaptopurine / Q000378:metabolism* / Q000493:pharmacokinetics; D008892:Milk / Q000201:enzymology* / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D015122:Mercaptopurine; D014969:Xanthine Oxidase