{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:23Z","timestamp":1787029343808,"version":"build-2736575974"},"reference-count":22,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Hydroxyurea (HU), also known as hydroxycarbamide, is an oral ribonucleotide reductase inhibitor. In 1999, the United States Food and Drug Administration (FDA) approved HU for the treatment of sickle cell disease (SCD). Since then, it has become the cornerstone in the management of SCD patients, helping to reduce vaso-occlusive crises, acute chest syndrome, the need for blood transfusions, hospitalizations and mortality. There is considerable variability among individuals in HU pharmacokinetic (Pk) parameters that can influence treatment efficacy and toxicity. The objective of this work is part of a clinical study aimed at investigating HU Pk and determining the optimal sampling time to estimate the Area Under the Curve (AUC) in SCD patients. Methods: HU plasma concentration in 80 patients at various time points (2, 4, 6, 24 h) following a 48-h drug washout was quantified using High-Pressure Liquid Chromatography (HPLC) coupled with an ultraviolet (UV) detection method previously described in the literature and adapted to new conditions with partial modifications. Results: The mean HU administered dose was 19.5 \u00b1 5.1 mg\/kg (range: 7.7\u201337.5 mg\/kg). The median AUC quantified in plasma patients was 101.3 mg\/L\/h (Interquartile Range (IQR): 72.5\u2013355.9) and it was not influenced by the weight-based dose. However, there was a strong positive correlation between AUC and Body Mass Index (BMI) as well as dose per Body Surface Area (BSA). Along with a three-point approach for AUC determination present in the literature, we show results obtained from a four-point sampling strategy, which is more useful and effective for better optimizing dose escalation to the maximum tolerated dose (MTD). Moreover, we observed that most patients achieved the maximum HU plasma concentration two hours after drug administration, regardless of age differences. Conclusions: HU treatment, which represents a milestone in the treatment of SCD due to its ability to reduce disease complications and improve patients\u2019 quality of life, requires careful monitoring to optimize the individual dose for saving potential side effects and\/or adverse events.<\/jats:p>","DOI":"10.3390\/ph17101386","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T11:19:18Z","timestamp":1729163958000},"page":"1386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hydroxyurea Pharmacokinetic Evaluation in Patients with Sickle Cell Disease"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1869-6762","authenticated-orcid":false,"given":"Daniela","family":"Di Grazia","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mirabella","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Chiara","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Caudana","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Maximillian Anthony","family":"Shelton Agar","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Zanatta","sequence":"additional","affiliation":[{"name":"Department of Economics and Statistics \u201cCognetti de Martiis\u201d, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4933-0011","authenticated-orcid":false,"given":"Sarah","family":"Allegra","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenni","family":"Bertello","sequence":"additional","affiliation":[{"name":"Microcythemia and Rare Haematological Diseases Center, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7249-2735","authenticated-orcid":false,"given":"Vincenzo","family":"Voi","sequence":"additional","affiliation":[{"name":"Microcythemia and Rare Haematological Diseases Center, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni Battista","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Microcythemia and Rare Haematological Diseases Center, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2727-2519","authenticated-orcid":false,"given":"Giuliana","family":"Abbadessa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-7802","authenticated-orcid":false,"given":"Silvia","family":"De Francia","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology \u201cFranco Ghezzo\u201d, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2022.10233","article-title":"Sickle Cell Disease: A Review","volume":"328","author":"Kavanagh","year":"2022","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e687","DOI":"10.1016\/S2352-3026(23)00182-5","article-title":"Sickle cell disease landscape and challenges in the EU: The ERN-EuroBloodNet perspective","volume":"10","author":"Colombatti","year":"2023","journal-title":"Lancet Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e585","DOI":"10.1016\/S2352-3026(23)00118-7","article-title":"Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000\u20132021: A systematic analysis from the Global Burden of Disease Study 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