{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T13:46:45Z","timestamp":1769089605420,"version":"3.49.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"apopharma inc (now chiesi) was the sponsor of the study."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:p>Patients with sickle cell disease (SCD) who undergo repeated blood transfusions often develop iron overload. Deferiprone (Ferriprox\u00ae) is an oral iron chelator indicated for the treatment of transfusional iron overload due to thalassemia syndromes and has been recently approved as a treatment for iron overload in adult and pediatric patients with SCD and other anemias. The present study aims to characterize the pharmacokinetic (PK) profile of deferiprone (DFP) in adult subjects with SCD. In this phase I, open-label study, subjects with SCD were administered a single 1500\u00a0mg dose of DFP. Blood and urine samples were collected for PK assessments of DFP and its main metabolite, deferiprone 3-O-glucuronide (DFP-G). Eight subjects were enrolled and completed the study. Following drug administration, serum levels of DFP and DFP-G rose to maximum concentrations at 1.0 and 2.8\u00a0h post-dose, respectively. The half-lives of DFP and DFP-G were 1.5 and 1.6\u00a0h, respectively. The majority of administered drug was metabolized and excreted as DFP-G, with less than 4% excreted unchanged in urine up to 10\u00a0h post-dose. Subjects received a safety assessment 7 (\u00b1\u20093) days post-dose. Two subjects reported mild adverse events unrelated to the study drug, and no other safety concerns were reported. The PK profile of DFP in SCD subjects is consistent with previous reports in healthy adult volunteers, suggesting no special dosing adjustments are indicated for this population. These findings provide valuable insight for treating iron overload in patients with SCD, who have limited chelation therapy treatment options (trial registration number: NCT01835496, date of registration: April 19, 2013).<\/jats:p>","DOI":"10.1007\/s00277-021-04728-0","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:03:16Z","timestamp":1641254596000},"page":"533-539","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The pharmacokinetic and safety profile of single-dose deferiprone in subjects with sickle cell disease"],"prefix":"10.1007","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1533-3815","authenticated-orcid":false,"given":"Denis","family":"Souli\u00e8res","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jules","family":"Mercier-Ross","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Fradette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Rozova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Chung","family":"Tsang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Tricta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"4728_CR1","unstructured":"World Health Organization (2015) Sickle cell disease. Factsheet [cited 2021 2 April]; Available from: https:\/\/www.afro.who.int\/health-topics\/sickle-cell-disease"},{"key":"4728_CR2","unstructured":"Centers for Disease Control and Prevention (2020) Data & statistics on sickle cell disease. Available from: https:\/\/www.cdc.gov\/ncbddd\/sicklecell\/data.html"},{"issue":"Suppl 1","key":"4728_CR3","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/ijlh.13023","volume":"41","author":"J Mburu","year":"2019","unstructured":"Mburu J, Odame I (2019) Sickle cell disease: reducing the global disease burden. Int J Lab Hematol 41(Suppl 1):82\u201388","journal-title":"Int J Lab Hematol"},{"issue":"Supplement 1","key":"4728_CR4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1182\/blood-2020-138895","volume":"136","author":"A Boye-Doe","year":"2020","unstructured":"Boye-Doe A et al (2020) The Grndad Registry: contemporary natural history data and an analysis of real-world patterns of use and limitations of disease modifying therapy in adults with SCD. Blood 136(Supplement 1):34\u201336","journal-title":"Blood"},{"issue":"5","key":"4728_CR5","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1111\/bjh.14575","volume":"177","author":"TD Coates","year":"2017","unstructured":"Coates TD, Wood JC (2017) How we manage iron overload in sickle cell patients. Br J Haematol 177(5):703\u2013716","journal-title":"Br J Haematol"},{"issue":"5834","key":"4728_CR6","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1136\/bmj.4.5834.206","volume":"4","author":"A Jacobs","year":"1972","unstructured":"Jacobs A et al (1972) Ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. Br Med J 4(5834):206\u2013208","journal-title":"Br Med J"},{"issue":"1 Suppl 1","key":"4728_CR7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/S0037-1963(01)90058-7","volume":"38","author":"SK Ballas","year":"2001","unstructured":"Ballas SK (2001) Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease. Semin Hematol 38(1 Suppl 1):30\u201336","journal-title":"Semin Hematol"},{"issue":"6","key":"4728_CR8","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/S0002-9343(99)80015-1","volume":"98","author":"MH Lee","year":"1995","unstructured":"Lee MH, Means RT Jr (1995) Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance. Am J Med 98(6):566\u2013571","journal-title":"Am J Med"},{"issue":"2","key":"4728_CR9","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1182\/bloodadvances.2019001143","volume":"4","author":"ST Chou","year":"2020","unstructured":"Chou ST et al (2020) American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv 4(2):327\u2013355","journal-title":"Blood Adv"},{"issue":"1","key":"4728_CR10","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/ajh.20402","volume":"80","author":"E Vichinsky","year":"2005","unstructured":"Vichinsky E et al (2005) Comparison of organ dysfunction in transfused patients with SCD or beta thalassemia. Am J Hematol 80(1):70\u201374","journal-title":"Am J Hematol"},{"key":"4728_CR11","unstructured":"(FDA), U.S.F.D.A. (2005) Jadenu\u00ae (deferasirox) tablets. Prescribing Information [cited 2021 2 April]; Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/206910s000lbl.pdf"},{"issue":"3","key":"4728_CR12","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrneph.2015.8","volume":"11","author":"KA Nath","year":"2015","unstructured":"Nath KA, Hebbel RP (2015) Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol 11(3):161\u2013171","journal-title":"Nat Rev Nephrol"},{"issue":"3S","key":"4728_CR13","doi-asserted-by":"publisher","first-page":"S28","DOI":"10.1016\/j.annemergmed.2020.08.009","volume":"76","author":"AB Payne","year":"2020","unstructured":"Payne AB et al (2020) Trends in Sickle cell disease-related mortality in the United States, 1979 to 2017. Ann Emerg Med 76(3S):S28\u2013S36","journal-title":"Ann Emerg Med"},{"key":"4728_CR14","unstructured":"Ferriprox\u00ae (deferiprone) tablets. , in Prescribing Information. 2011, United States Food and Drug Administration"},{"issue":"4","key":"4728_CR15","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1111\/bcp.13037","volume":"82","author":"C Fradette","year":"2016","unstructured":"Fradette C et al (2016) Effects of renal impairment on the pharmacokinetics of orally administered deferiprone. Br J Clin Pharmacol 82(4):994\u20131001","journal-title":"Br J Clin Pharmacol"},{"issue":"6","key":"4728_CR16","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1111\/j.1365-2125.2008.03103.x","volume":"65","author":"LM Limenta","year":"2008","unstructured":"Limenta LM et al (2008) UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy volunteers. Br J Clin Pharmacol 65(6):908\u2013916","journal-title":"Br J Clin Pharmacol"},{"issue":"11","key":"4728_CR17","doi-asserted-by":"publisher","first-page":"2703","DOI":"10.1182\/blood.V106.11.2703.2703","volume":"106","author":"EV Haverfield","year":"2005","unstructured":"Haverfield EV et al (2005) Pharmacogenomics of deferiprone metabolism. Blood 106(11):2703\u20132703","journal-title":"Blood"},{"issue":"6","key":"4728_CR18","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1016\/0016-5085(86)90276-3","volume":"90","author":"TT Schubert","year":"1986","unstructured":"Schubert TT (1986) Hepatobiliary system in sickle cell disease. Gastroenterology 90(6):2013\u20132021","journal-title":"Gastroenterology"},{"issue":"3","key":"4728_CR19","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4291\/wjgp.v8.i3.108","volume":"8","author":"R Shah","year":"2017","unstructured":"Shah R, Taborda C, Chawla S (2017) Acute and chronic hepatobiliary manifestations of sickle cell disease: a review. World J Gastrointest Pathophysiol 8(3):108\u2013116","journal-title":"World J Gastrointest Pathophysiol"},{"key":"4728_CR20","unstructured":"Electronic Medicines Compendium (EMC). Desferal Vials. Summary of product characteristics 6 August 2020 [cited 2021 2 April]; Available from: https:\/\/www.medicines.org.uk\/emc\/product\/3813\/smpc"},{"key":"4728_CR21","unstructured":"Electronic Medicines Compendium (EMC) (2020) Exjade. Summary of product characteristics [cited 2021 2 April]"},{"key":"4728_CR22","unstructured":"Electronic Medicines Compendium (EMC). Ferriprox. Summary of product characteristics [cited 2021 2 April]; Available from: https:\/\/www.medicines.org.uk\/emc\/product\/10908\/smpc"},{"issue":"4","key":"4728_CR23","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1093\/ckj\/sfx027","volume":"10","author":"V Audard","year":"2017","unstructured":"Audard V, Bartolucci P, Stehle T (2017) Sickle cell disease and albuminuria: recent advances in our understanding of sickle cell nephropathy. Clin Kidney J 10(4):475\u2013478","journal-title":"Clin Kidney J"},{"issue":"9","key":"4728_CR24","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1002\/ajh.23762","volume":"89","author":"KI Ataga","year":"2014","unstructured":"Ataga KI, Derebail VK, Archer DR (2014) The glomerulopathy of sickle cell disease. Am J Hematol 89(9):907\u2013914","journal-title":"Am J Hematol"},{"key":"4728_CR25","unstructured":"European Medicines Agency (EMA) (2021) Ferriprox. Summary of product characteristics. [cited 2021 2 April]; Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/ferriprox-epar-product-information_en.pdf"},{"key":"4728_CR26","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-122062","volume-title":"Randomized controlled trial of the efficacy and safety of deferiprone in iron-overloaded patients with sickle cell disease or other anemias","author":"JL Kwiatkowski","year":"2019","unstructured":"Kwiatkowski JL et al (2019) Randomized controlled trial of the efficacy and safety of deferiprone in iron-overloaded patients with sickle cell disease or other anemias. American Society of Hematology, Washington, DC"},{"issue":"6","key":"4728_CR27","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.3390\/cells9061456","volume":"9","author":"GJ Kontoghiorghes","year":"2020","unstructured":"Kontoghiorghes GJ, Kontoghiorghe CN (2020) Iron and chelation in biochemistry and medicine: new approaches to controlling iron metabolism and treating related diseases. Cells 9(6):1456","journal-title":"Cells"},{"issue":"9","key":"4728_CR28","doi-asserted-by":"publisher","first-page":"3242","DOI":"10.1182\/blood-2005-02-0460","volume":"106","author":"H Glickstein","year":"2005","unstructured":"Glickstein H et al (2005) Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 106(9):3242\u20133250","journal-title":"Blood"},{"issue":"11","key":"4728_CR29","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/ajh.20685","volume":"81","author":"DS Darbari","year":"2006","unstructured":"Darbari DS et al (2006) Circumstances of death in adult sickle cell disease patients. Am J Hematol 81(11):858\u2013863","journal-title":"Am J Hematol"},{"issue":"4","key":"4728_CR30","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.hoc.2014.04.002","volume":"28","author":"JC Wood","year":"2014","unstructured":"Wood JC (2014) Use of magnetic resonance imaging to monitor iron overload. Hematol Oncol Clin North Am 28(4):747\u201364 (vii)","journal-title":"Hematol Oncol Clin North Am"},{"key":"4728_CR31","unstructured":"Use, I.C.F.H.O.T.R.F.P.F.H. (2018) M10 bioanalytical method validation. [cited 2021 October 7]; Available from: https:\/\/www.fda.gov\/media\/128343\/download"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04728-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-021-04728-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-021-04728-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T03:06:54Z","timestamp":1643857614000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-021-04728-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["4728"],"URL":"https:\/\/doi.org\/10.1007\/s00277-021-04728-0","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]},"assertion":[{"value":"28 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) This study was conducted in accordance with the accepted version of the Declaration of Helsinki 1975, as revised in 2008. The study was approved by Centre Hospitalier Universit\u00e9 de Montr\u00e9al (CHUM) ethics committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All of the authors have approved of the final submitted version.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Denis Souli\u00e8res is a participant on ApoPharma advisory board and received ApoPharma institutional grant.Jules Mercier-Ross has no conflict of interest to declare.Caroline Fradette is an employee of Chiesi Canada.Anna Rozova is an employee of Chiesi Canada.Yu Chung Tsang is an employee of Apotex Inc., which is the contract manufacturer of the drug product (i.e., FERRIPROX\u00ae) used in the study reported in this manuscript.Fernando Tricta is an employee of Chiesi Canada.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}