Assuntos
Anemia Falciforme/tratamento farmacológico , Benzaldeídos/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Fármacos Hematológicos/farmacologia , Hemoglobina Falciforme/metabolismo , Modelos Biológicos , Oxigênio/sangue , Oxiemoglobinas/metabolismo , Pirazinas/farmacologia , Pirazóis/farmacologia , 2,3-Difosfoglicerato/sangue , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Benzaldeídos/efeitos adversos , Benzaldeídos/uso terapêutico , Transtornos Cerebrovasculares/induzido quimicamente , Transtornos Cerebrovasculares/etiologia , Eritrócitos Anormais/metabolismo , Hematócrito , Fármacos Hematológicos/efeitos adversos , Fármacos Hematológicos/uso terapêutico , Hemoglobina Falciforme/química , Hemólise/efeitos dos fármacos , Humanos , Hipóxia/prevenção & controle , Microcirculação/efeitos dos fármacos , Especificidade de Órgãos , Polimerização/efeitos dos fármacos , Ligação Proteica , Pirazinas/efeitos adversos , Pirazinas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Medição de RiscoRESUMO
The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch-conjugated DFO (S-DFO; 40SD02), a high-molecular-weight iron chelator possessing prolonged vascular retention. Single doses of S-DFO were infused intravenously into groups of four transfusion-dependent patients with beta-thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug-related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug-related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1.31 mg of iron/kg (range 0.79-1.90 mg/kg) over 1 week, with residual iron-binding capacity present in the plasma for over 6 d. In summary, treatment with S-DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.