Population pharmacokinetics of hydroxyurea for children and adolescents with sickle cell disease

Paweł Wiczling*, Robert I Liem, Julie A. Panepinto, Uttam Garg, Susan M. Abdel-Rahman, Gregory L. Kearns, Kathleen A. Neville

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 0.222hour. The typical apparent volume of distribution was 21.8L and the apparent systemic clearance was 6.88L/h for an average weight patient of 30.7kg. 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 6hours post-dose and AUC with the most significant (R2=0.71) observed at 1.5hours. 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 1.5hours after an oral dose of the drug were highly predictive of systemic drug exposure.

Original languageEnglish (US)
Pages (from-to)1016-1022
Number of pages7
JournalJournal of Clinical Pharmacology
Volume54
Issue number9
DOIs
StatePublished - Jan 1 2014

Keywords

  • hydroxyurea
  • sickle cell disease
  • therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Medicine(all)

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    Wiczling, P., Liem, R. I., Panepinto, J. A., Garg, U., Abdel-Rahman, S. M., Kearns, G. L., & Neville, K. A. (2014). Population pharmacokinetics of hydroxyurea for children and adolescents with sickle cell disease. Journal of Clinical Pharmacology, 54(9), 1016-1022. https://doi.org/10.1002/jcph.303