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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4009-4013. Prepublished online as a Blood First Edition Paper on September 1, 2009; DOI 10.1182/blood-2009-05-222729. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2009-05-222729v1 114/19/4009    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Chirnomas, D. Articles by Neufeld, E. J. PubMed PubMed Citation Articles by Chirnomas, D. Articles by Neufeld, E. J. Related Collections Red Cells, Iron, and Erythropoiesis Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Deferasirox pharmacokinetics in patients with adequate versus inadequate response Deborah Chirnomas13, Amber Lynn Smith1, Jennifer Braunstein1, Yaron Finkelstein2,4,5, Luis Pereira4, Anke K. Bergmann1,2, Frederick D. Grant2,6, Carole Paley7, Michael Shannon2,4, and Ellis J. Neufeld13 1 Hematology/Oncology, Children's Hospital Boston, MA; 2 Harvard Medical School, Boston, MA; 3 Dana-Farber Cancer Institute, Boston, MA; 4 Clinical Pharmacology Unit, Children's Hospital Boston, MA; 5 Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, Toronto, ON; 6 Division of Nuclear Medicine, Children's Hospital Boston, MA; and 7 Novartis Pharmaceuticals Corporation, East Hanover, NJ Tens of thousands of transfusion-dependent (eg, thalassemia) patients worldwide suffer from chronic iron overload and its potentially fatal complications. The oral iron chelator deferasirox has become commercially available in many countries since 2006. Although this alternative to parenteral deferoxamine has been a major advance for patients with transfusional hemosiderosis, a proportion of patients have suboptimal response to the maximum approved doses (30 mg/kg per day), and do not achieve negative iron balance. We performed a prospective study of oral deferasirox pharmacokinetics (PK), comparing 10 transfused patients with inadequate deferasirox response (rising ferritin trend or rising liver iron on deferasirox doses > 30 mg/kg per day) with control transfusion-dependent patients (n = 5) with adequate response. Subjects were admitted for 4 assessments: deferoxamine infusion and urinary iron measurement to assess readily chelatable iron; quantitative hepatobiliary scintigraphy to assess hepatic uptake and excretion of chelate; a 24-hour deferasirox PK study following a single 35-mg/kg dose of oral deferasirox; and pharmacogenomic analysis. Patients with inadequate response to deferasirox had significantly lower systemic drug exposure compared with control patients (P < .00001). Cmax, volume of distribution/bioavailability (Vd/F), and elimination half-life (t1/2) were not different between the groups, suggesting bioavailability as the likely discriminant. Effective dosing regimens for inadequately responding patients to deferasirox must be determined. This trial has been registered at http://www.clinicaltrials.gov under identifier NCT00749515 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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