Influence of Food Intake on Bioavailability of Oral 6-Mercaptopurine in Children with Acute Lymphoblastic Leukemia

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Abstract
Plasma levels of 6-mercaptopurine (6-MP) were measured after oral administration in 17 children with acute lymphoblastic leukemia (ALL). In the fasting state or after a breakfast consisting of 250 ml milk and 50 g biscuits, 6-MP was administered at a dose of 75 mg/m2. In patients studied in a fasting state, the mean time to plasma peak (tmax) level was 1.2 h, whereas in patient studied after breakfast the mean tmax was 2.3 h. This difference is statistically significant (p < 0.001). Moreover, the 6-MP peak plasma concentration (cmax) and the areas under the plasma concentration time curves (AUC) were significantly reduced when the drug was administered after breakfast. The mean cmax ± SD were 0.98 ± 0.54 μM and 0.63 ± 0.48 μM, respectively (p < 0.05). The mean 6-MP AUC ± SD in patients studied in a fasting state and after breakfast were 143 ± 69 μM min and 105 ± 68 μM, respectively (p < 0.01). These results indicate that 6-MP should be taken in a fasting state to optimize drug absorption in children undergoing chemotherapy for ALL.