Oral 6-mercaptopurine in childhood leukemia: parent drug pharmacokinetics and active metabolite concentrations.

Abstract

6-Mercaptopurine (6MP) pharmacokinetics and red blood cell 6-thioguanine nucleotide (TGN) concentrations were studied in 19 children receiving remission maintenance treatment for lymphoblastic leukemia. There was a high interpatient variation in all the pharmacokinetic parameters measured. The pharmacokinetic parameters measured in two children who subsequently had relapses were within the 95% confidence limits of the 17 other children. There was no difference in 6MP pharmacokinetic parameters with respect to neutropenia either after or before the study. The children who developed neutropenia 10 to 19 days after study had significantly higher TGN concentrations (U = 8; P less than 0.001) and had spent a longer time receiving reduced 6MP dosage in the 12 weeks before the study (U = 19.5; P less than 0.025). TGN concentrations are a better index of a child's ability to form active cytotoxic metabolites than 6MP dose or plasma concentrations.

• Authors: L Lennard, D Keen, J S Lilleyman
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 40 Issue 3 Pg. 287-92 (Sep 1986) ISSN: 0009-9236 [Print] United States
• PMID: 3461899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mercaptopurine
• Thioguanine

Topics

• Administration, Oral
• Child
• Child, Preschool
• Erythrocytes (analysis)
• Humans
• Infant
• Kinetics
• Leukemia, Lymphoid (blood, drug therapy)
• Mercaptopurine (administration & dosage, blood)
• Thioguanine (blood)