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Plasma concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Ten children (nine with acute lymphatic leukemia) were studied on 2 consecutive days after oral intake of 6-MP. On one day the drug was administered in the fasting state and on the other (in random order) together with breakfast. The peak plasma concentrations of 6-MP after the dose intake with breakfast in percent of that in the fasting state (meal in % of fasting for each individual) varied between 33 and 181% (mean 111), and the area under the plasma concentration-time curve varied between 47 and 186% (mean 103). Thus, there were considerable variations among patients, but, for the group as a whole, there were no statistically significant differences between the two experimental conditions. This study cannot therefore form the basis for a recommendation as to whether 6-MP should be administered on an empty stomach or together with food.

Plasma and erythrocyte concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Eleven children (9 with acute lymphatic leukemia) were studied after oral intake of 6-MP doses ranging between 31 and 128 mg/m2 body surface area. The concentrations of 6-MP in plasma were found to vary considerably between patients even after dose normalization to 75 mg/m2. After dose normalization the mean peak plasma concentration was 0.68 microM (range 0.12-1.38) and the area under the plasma concentration-time curve (AUC) was 1.37 microM.h (range 0.12-3.04). The mean time taken to reach the peak concentration was 1.3 h (range 1-2), and the half-life of elimination was 1.8 h (range 0.6-2.5). No patient had detectable 6-MP concentrations 12 h after dose intake. The concentrations of 6-MP tended to be higher in erythrocytes than in plasma. The mean peak concentration in erythrocytes was 131% and the AUC 145% of that found in plasma. The mean half-life of elimination from erythrocytes was 2.0 h (range 0.7-2.8). These data indicate that 6-MP can pass through all membranes rapidly to reach intracellular concentrations equal to or even higher than in plasma. In summary, marked interindividual differences in pharmacokinetics were found, probably due to highly variable bioavailability of oral 6-MP. Further studies are needed to determine whether measurements of plasma concentrations of 6-MP can be used to optimize maintenance treatment of childhood leukemia.