Population pharmacokinetics of hydroxyurea for children and adolescents with sickle cell disease. J Clin Pharmacol 2014 Sep;54(9):1016-22
Date
04/15/2014Pubmed ID
24729271DOI
10.1002/jcph.303Scopus ID
2-s2.0-84905510021 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
The objective of this study was to develop a population pharmacokinetic (PK) model sufficient to describe hydroxyurea (HU) concentrations in serum and urine following oral drug administration in pediatric patients with sickle cell disease. Additionally, the measured hydroxyurea concentrations for particular sampling time were correlated with exposure measures (AUC) to find the most predictive relationship. Hydroxyurea concentrations were determined in 21 subjects. Using a population nonlinear mixed-effect modeling, the HU PK was best described by a one-compartment model with two elimination pathways (metabolic and renal) and a transit compartment absorption. The typical mean absorption time was 0.222 hour. The typical apparent volume of distribution was 21.8 L and the apparent systemic clearance was 6.88 L/h for an average weight patient of 30.7 kg. The 50% of the HU dose was renally excreted. Linear correlations were apparent between the plasma HU concentration at 1, 1.5, 2, 4, and 6 hours post-dose and AUC with the most significant (R(2) = 0.71) observed at 1.5 hours. A population PK model was successful in describing HU disposition in plasma and urine. Data from the model also demonstrated that HU plasma concentrations at 1.5 hours after an oral dose of the drug were highly predictive of systemic drug exposure.
Author List
Wiczling P, Liem RI, Panepinto JA, Garg U, Abdel-Rahman SM, Kearns GL, Neville KAMESH terms used to index this publication - Major topics in bold
Administration, OralAdolescent
Anemia, Sickle Cell
Antisickling Agents
Area Under Curve
Child
Child, Preschool
Female
Humans
Hydroxyurea
Male
Models, Biological