Hydroxyurea (HU) is approved by the United States Food and Drug Administration (FDA) to treat adults with sickle cell anemia. Hydroxyurea has also been tested and used with children with sickle cell anemia. However, there are not many studies describing the disposition of drug in children less than 5 years old. The FDA has requested this study to better understand how children ages 2 to 17 years with sickle anemia absorb and eliminate the drug (this is called pharmacokinetics). The investigators will measure how much Hydroxyurea (HU) gets into the bloodstream at different time points after taking this medication.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Masking
NONE
Enrollment
39
20mg/kg of Hydroxyurea or the patient's standard daily dose
Children's Hospital of Alabama
Birmingham, Alabama, United States
Children's Memorial Hospital (Northwestern University)
Chicago, Illinois, United States
Columbia University Medical Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
UT Southwestern University Hospital
Dallas, Texas, United States
Children's Hospital of Wisconsin
Wauwatosa, Wisconsin, United States
Composite of Pharmacokinetics
Cmax, Area Under Curve, Tmax. Also, the following pharmacokinetic parameters will be derived for each participant using standard techniques: Apparent absorption rate constant, Apparent terminal elimination rate constant, Apparent steady state volume of distribution, Apparent plasma clearance. A compartment, model-based, classical fitting paradigm of the plasma concentration vs. time data will be applied to each subjects' data. Standard goodness of fit criteria will be employed. Subjects aged greater than or equal to 2 and less than or equal to 17 years.
Time frame: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose
Pharmacokinetics of HU
To evaluate the relative bioavailability of a liquid HU formulation (100mg/mL0 in participants ages greater that 5 and less than or equal to 17 years of age compared to standard therapy utilizing Droxia 200mg capsules
Time frame: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose
Bioavailability of HU
Relative bioavailability of liquid HU formulation in comparison to Droxia® capsules will be assessed according to published FDA Bioequivalence Guidance Subjects aged greater than 5 and less than or equal to 17 years Derived steady-state PK parameters after multiple doses of liquid HU (AUC(0-12), AUC(0-∞), Cmax, Tmax, and t½) Steady-state plasma(PK)parameters for liquid formulation of HU will be evaluated Subjects ages greater than or equal to 2 and less than or equal to 5 years will receive doses of 20mg/kg/day for at least 4 consecutive days before evaluation of the steady-state parameters
Time frame: predose, 0.17, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8 hours post-dose
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