Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.
Journal Article (Clinical Trial;Journal Article;Multicenter Study)
Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA.
Full Text
Duke Authors
Cited Authors
- Estepp, JH; Melloni, C; Thornburg, CD; Wiczling, P; Rogers, Z; Rothman, JA; Green, NS; Liem, R; Brandow, AM; Crary, SE; Howard, TH; Morris, MH; Lewandowski, A; Garg, U; Jusko, WJ; Neville, KA; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee,
Published Date
- March 2016
Published In
Volume / Issue
- 56 / 3
Start / End Page
- 298 - 306
PubMed ID
- 26201504
Pubmed Central ID
- PMC4892120
Electronic International Standard Serial Number (EISSN)
- 1552-4604
Digital Object Identifier (DOI)
- 10.1002/jcph.598
Language
- eng
Conference Location
- England