1991 Volume 17 Issue 4 Pages 257-264
In order to improve the bioavailability of 6-mercaptopurine (6-MP), the elixir and two kinds of suppositories (Witepsol (WH) base and macrogol (MC) base) of 6-MP were prepared and administered to a child with acute lymphoblastic leukemia (ALL) in a balanced crossover design. Plasma levels and the area under the plasm concentration-time curve (AUC) values for 6-MP were determined following the powder, elixir and suppositories administrations of 6-MP. Compared with the AUC value after the powder administration, the relative bioavailabilities (Fret) for the elixir and suppositories were evaluated, respectively. The concentration of 6-MP in the elixir was prepared to 0.25%.The suppositories of 6-MP were prepared by the fusion method and the content was 20 mg/g/one suppository. The release of 6-MP from the suppositories was examined by the dissolution test in vitro before the clinical study. The release ratio of 6-MP was higher from the MC base suppository than from the WH base suppository. 6-MP was administered orally (50 mg/m2) and rectally (30 mg/m2) to the child with ALL, respectively. The plasma levels of 6-MP were determined by the high-performance liquid chromatography method. The AUC values (ng·hr/ml) from the powder, elixir, WH suppository and MC suppository administrations were 82.3, 204.0, 197.0 and 714.4, respectively.The Frel for the elixir, WH suppository and MC suppository were 2.48, 3.99 and 14.47, respectively, that was extremely increased by the MC suppository administration.
This finding indicates that the rectal administration by the MC suppository of 6-MP could avoid the first-pass metabolism of this drug, and that this rectal administration of 6-MP will be effective on the treatment of children with ALL, especially for the patients with nausea and/or vomiting.
