Faculty Collaboration Database

Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia. J Clin Pharmacol 2016 Mar;56(3):298-306

Date

07/24/2015

Pubmed ID

26201504

Pubmed Central ID

PMC4892120

DOI

10.1002/jcph.598

Scopus ID

2-s2.0-84958113265 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

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.

Author List

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

Author

Amanda Brandow DO Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Anemia, Sickle Cell
Antisickling Agents
Capsules
Child
Child, Preschool
Female
Humans
Hydroxyurea
Male
Prospective Studies
Solutions
Therapeutic Equivalency