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. 2019 Oct 16;8(10):1701.
doi: 10.3390/jcm8101701.

Optimizing Hydroxyurea Treatment for Sickle Cell Disease Patients: The Pharmacokinetic Approach

Charlotte Nazon  1 , Amelia-Naomi Sabo  2   3 , Guillaume Becker  4   5 , Jean-Marc Lessinger  6 , Véronique Kemmel  7   8 , Catherine Paillard  9   10
Affiliations

Optimizing Hydroxyurea Treatment for Sickle Cell Disease Patients: The Pharmacokinetic Approach

Charlotte Nazon et al. J Clin Med. .

Abstract

Background: Hydroxyurea (HU) is a FDA- and EMA-approved drug that earned an important place in the treatment of patients with severe sickle cell anemia (SCA) by showing its efficacy in many studies. This medication is still underused due to fears of physicians and families and must be optimized.

Methods: We analyzed our population and identified HU pharmacokinetic (PK) parameters in order to adapt treatment in the future. Working with a pediatric population, we searched for the most indicative sampling time to reduce the number of samples needed.

Results: Nine children treated by HU for severe SCA were included for this PK study. HU quantification was made using a validated gas chromatography/mass spectrometry (GC/MS) method. Biological parameters (of effectiveness and compliance) and clinical data were collected. None of the nine children reached the therapeutic target defined by Dong et al. as an area under the curve (AUC) = 115 h.mg/L; four patients were suspected to be non-compliant. Only two patients had an HbF over 20%. The 2 h sample was predictive of the medication exposure (r2 = 0.887).

Conclusions: It is urgent to be more efficient in the treatment of SCA, and pharmacokinetics can be an important asset in SCA patients.

Keywords: hydroxyurea; pharmacokinetics; sickle cell anemia; sickle cell disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mean HU (±standard deviation) concentration–time plot (n = 9 patients).
Figure 2
Figure 2
(a) Relation between area under the curve (AUC) and HU concentration-time for 2-h samples; y = 3.5701x + 11.727. (b) Relation between AUC and HU concentration-time for 4-h samples; y = 4.4637x + 28.402.
See this image and copyright information in PMC

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