title: Rectal bioavailability of 6-mercaptopurine in children with acute lymphoblastic leukaemia: partial avoidance of "first-pass" metabolism.
abstract: Plasma levels and the area under the plasma concentration-time curve (AUC) values of 6-mercaptopurine (6-MP) were determined in a balanced crossover study of oral (powder) and rectal (macrogol suppository) administration to 5 children with acute lymphoblastic leukaemia (ALL). The AUC (538.6 ng.h.ml-1) after the rectal dose of 30 mg/m2 was approximately 1.5-times of that (365.5 ng.h.ml-1) after the oral dose of 87.5 mg/m2. The coefficients of variation of interindividual variability of the AUCs were 21.5% and 32.3%, respectively. The relative bioavailability of the macrogol suppository compared to the powder was approximately 4.39. These findings indicate that rectal administration of 6-MP could avoid the first-pass effect of this drug in the alimentary canal and/or liver, resulting in a large AUC of 6-MP, and so could reduce interindividual variability in plasma 6-MP concentrations. Rectal administration of 6-MP may be more effective than empirical oral dosing for the treatment of children with ALL, especially for patients with nausea and/or vomiting.
authors.affiliation: Department of Pharmacy, Meiji College of Pharmacy, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: H
authors.initials: H
authors.lastname: Uchida
authors.forename: S
authors.initials: S
authors.lastname: Egi
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: K
authors.initials: K
authors.lastname: Mohri
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000293:Adolescent; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: D015122:Mercaptopurine