PMID: 1861221Aug 1, 1991Paper

Dose-dependent kinetics of orally administered 6-mercaptopurine in children with leukemia

The Journal of Pediatrics
Y KatoT Ishizaki

Abstract

To determine whether the pharmacokinetics of 6-mercaptopurine (6-MP) would show dose dependency, we studied three different single oral doses in eight children (aged 3.6 to 15.1 years) with acute leukemia in remission. Marked interindividual differences in maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were observed when children received the 50 mg/m2 dose. This variability decreased when the doses were increased. Six of the eight children showed a disproportionate increase in the AUC with increasing doses; the other two had a proportionate relationship between the AUC and dose. Overall mean (+/- SD) Cmax and AUC values increased disproportionately (88 +/- 123, to 326 +/- 194, to 653 +/- 344 ng/ml for Cmax, and 147 +/- 180, to 451 +/- 177, to 1291 +/- 415 ng/ml per hour for AUC, respectively) when the dose increased from 50 to 87.5 mg/m2 and then to 175 mg/m2. The results suggest that a saturable first-pass metabolism of oral 6-MP occurs with increasing oral doses in some, but not all, children. Whether and to what extent this pharmacokinetic character of oral 6-MP affects the interindividual difference in systemic exposure to the drug in children with leukemia receiving mainten...Continue Reading

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Citations

Oct 12, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·Y SuM V Relling
Apr 11, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Harpreet K DhaliwalLynne Lennard
Apr 15, 2011·Cancer Treatment Reviews·Hendrik van den BergJos H Beijnen
Dec 8, 2004·Critical Reviews in Oncology/hematology·E GroningerS S N de Graaf
May 5, 2020·Alimentary Pharmacology & Therapeutics·Albert J Czaja

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