A novel 6-mercaptopurine oral liquid formulation for pediatric acute lymphoblastic leukemia patients - results of a randomized clinical trial

作者：Hanff Lidwien M^*; Mathot Ron A A; Smeets Oscar; Postma Doerine J; Ramnarain Satianand; Vermes Andras; Pieters Rob; Zwaan C Michel

来源：International Journal of Clinical Pharmacology and Therapeutics, 2014, 52(8): 653-662.

DOI：10.5414/CP202054

• mercaptopurine
• drug formulation
• acute lymphoblastic leukemia
• pediatric pharmacology

Objective: Pediatric patients with acute lymphoblastic leukemia (ALL) are treated with oral 6-mercaptopurine (6MP) for nearly 2 years, but no pediatric formulation has been available. In this study, an oral 6MP liquid suitable for pediatric use was developed and tested in the target population. Method: A randomized cross-over study was performed in 20 pediatric ALL patients (age 1.9 - 14.6 years), comparing pharmacokinetics and pharmacodynamics of a newly developed 6MP liquid formulation to 6MP capsules, both taken orally for 4 weeks. Results: Based upon trough levels of the principal active metabolite, 6-thioguanine nucleotides (6-TGN), a relative bioavailability of the liquid vs. capsules of 1.01 was found (90% CI 0.86 - 1.20), demonstrating bioequivalence. This was supported by the similarly observed 6MP dosages needed for leucocyte depletion, for both formulations (35 mg/day (range 10 - 115 mg)). 75% of the parents/patients (p = 0.005) preferred the oral liquid over the capsules because of the ease of administration. Conclusion: We conclude that the novel 6MP liquid is a promising treatment for ALL.

• 出版日期2014-8