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Article

Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease

1
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA
2
Departments of Global Pediatric Medicine and Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
3
Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Koyo Nishida
Pharmaceutics 2022, 14(5), 1065; https://doi.org/10.3390/pharmaceutics14051065
Received: 13 March 2022 / Revised: 13 April 2022 / Accepted: 19 April 2022 / Published: 16 May 2022
(This article belongs to the Section Pharmacokinetics and Pharmacodynamics)
Sickle cell disease (SCD) is a chronic hemolytic anemia affecting millions worldwide with acute and chronic clinical manifestations and early mortality. While hydroxyurea (HU) and other treatment strategies managed to ameliorate disease severity, high inter-individual variability in clinical response and a lack of an ability to predict those variations need to be addressed to maximize the clinical efficacy of HU. We developed pharmacokinetics (PK) and pharmacodynamics (PD) models to study the dosing, efficacy, toxicity, and clinical response of HU treatment in more than eighty children with SCD. The clinical PK parameters were used to model the HU plasma concentration for a 24 h period, and the estimated daily average HU plasma concentration was used as an input to our PD models with approximately 1 to 9 years of data connecting drug exposure with drug response. We modeled the biomarkers mean cell volume and fetal hemoglobin to study treatment efficacy. For myelosuppression, we modeled red blood cells and absolute neutrophil count. Our models provided excellent fits for individuals with known or correctly inferred adherence. Our models can be used to determine the optimal dosing regimens and study the effect of non-adherence on HU-treated individuals. View Full-Text
Keywords: sickle cell disease; hydroxyurea; PK-PD; fetal hemoglobin; mean cell volume sickle cell disease; hydroxyurea; PK-PD; fetal hemoglobin; mean cell volume
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MDPI and ACS Style

Pandey, A.; Estepp, J.H.; Raja, R.; Kang, G.; Ramkrishna, D. Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease. Pharmaceutics 2022, 14, 1065. https://doi.org/10.3390/pharmaceutics14051065

AMA Style

Pandey A, Estepp JH, Raja R, Kang G, Ramkrishna D. Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease. Pharmaceutics. 2022; 14(5):1065. https://doi.org/10.3390/pharmaceutics14051065

Chicago/Turabian Style

Pandey, Akancha, Jeremie H. Estepp, Rubesh Raja, Guolian Kang, and Doraiswami Ramkrishna. 2022. "Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease" Pharmaceutics 14, no. 5: 1065. https://doi.org/10.3390/pharmaceutics14051065

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