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J Clin Pharmacol. 2016 Mar;56(3):298-306. doi: 10.1002/jcph.598. Epub 2015 Oct 15.

Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

Author information

1
Departments of Hematology and Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
2
Division of Clinical Pharmacology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
3
Department of Pediatrics, University of California-San Diego, La Jolla, CA, USA.
4
Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland.
5
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
6
Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
7
Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Columbia University Medical Center, New York, NY, USA.
8
Division of Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
9
Section of Pediatric Hematology/Oncology, Medical College of Wisconsin, and Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI, USA.
10
Division of Pediatric Hematology-Oncology, University of Arkansas for Medical Sciences/Arkansas Children's Hospital, Little Rock, AR, USA.
11
Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.
12
Duke Clinical Research Institute, Durham, NC, USA.
13
The Emmes Corporation, Rockville, MD, USA.
14
Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.
15
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA.
16
Section of Pharmacology and Toxicology, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.

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.

KEYWORDS:

bioequivalent; hydroxyurea. children; sickle cell anemia

PMID:
26201504
PMCID:
PMC4892120
[Available on 2017-03-01]
DOI:
10.1002/jcph.598
[Indexed for MEDLINE]
Free PMC Article

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