Abstract

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. capsulesof 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.

Author Details

Authors

• Lidwien M. Hanff¹
• Ron A.A. Mathot²
• Oscar Smeets³
• Doerine J. Postma³
• Satianand Ramnarain⁴
• Andras Vermes¹
• Rob Pieters⁴
• C. Michel Zwaan⁴

Departments

• ¹ Department of Hospital Pharmacy, Erasmus MC, Rotterdam,
• ² Department of Hospital Pharmacy, Academic Medical Center, Amsterdam,
• ³ Laboratory of Dutch Pharmacists, Royal Dutch Pharmacists Association, Den Haag, and
• ⁴ Department of Pediatric Oncology, Erasmus MC – Sophia Children’s Hospital, Rotterdam, The Netherlands

Address

L.M.Hanff, PharmD, PhD
Department of Hospital Pharmacy Erasmus MC
PO Box 2040, 3000 CA Rotterdam, The Netherlands
Email: [email protected]

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