---

Background and purpose: Patients with Beta thalassemia major need consistent blood transfusion from early years of life. Deferasirox is used as an oral chelating agent (once daily) to excrete excess iron. This study aimed to compare the efficacy of deferasirox twice daily and the usual once daily dosing. Materials and methods: This before after clinical trial was performed in 2013-2014 in patients who were at least 2 years of age and received only deferasirox as the chelating agent. All patients had received deferasirox for at least six month once daily. The last ferritin before entering the study and the mean deferasirox daily dose during the previous six months were considered as baseline ferritin and deferasirox dose, respectively. Laboratory tests were performed including CBC-diff, serum ferritin, Creatinine (Cr), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) to evaluate the efficacy and safety of deferasirox. Results: A total of 21 transfusion-dependent patients (mean age: 21±6 years old) were included of whom 67% were male. The mean ferritin level decreased significantly from 1814± 922 ng/ml to 1472± 907 ng/ml (P= 0.02). There were no any significant changes in AST, ALT and Cr levels compared to baseline values. Conclusion: Twice daily dosing of deferasirox was associated with more decrease in ferritin level compared to baseline single daily dose values without any hepatic or renal adverse effects.

---

Background and purpose: Exjade^® is developed by Novartis pharmaceutical company and contains the active substance deferasirox, an orally active iron chelator for treatment of chronic iron overload following blood transfusions such as beta thalassemia. The aim of this study was to compare the physicochemical characteristics of branded generic product of deferasirox, Osveral^®, produced by Osveh pharmaceutical company (in Iran) with the original brand.

Materials and methods: Three doses (125, 250 and 500 mg) of deferasirox reference tablets (Exjade^®) were compared with the same doses of Osveral^®. Three batches of each product were randomly selected and physicochemical evaluations including appearance, disintegration time, hardness, assay, in vitro drug release and content uniformity were determined. Also, the similarity factor was calculated based on ICH (International Conference Harmonization) and Food and Drug Administration (FDA) guidelines. The drug entrapped in the tablets was determined by HPLC. The dissolution rates were measured in solution media (phosphate buffered and sodium Lauryl sulfate at 37 ºC) within 30 min by USP apparatus II (Paddle) at 50 RPM speed after 5, 10, 20 and 30 min intervals.

Results: The results indicated that physicochemical properties of Osveral^® were similar to those of Exjade^®. Disintegration time for both products was less than 1 min and drug assay was between 90 – 110%. In addition, the similarity factor was more than 50% for all doses.

Conclusion: Osveral^® is a reliable branded generic formulation of deferasirox for treatment of chronic iron overload states.

---

Background and purpose: Cancer is one of the causes of mortality worldwide. Evidence suggests that iron depletion by a chelator agent suppresses the development of some cancer cells. Deferasirox is shown to have anticancer properties. This research aims to synthesize and evaluate the effects of deferasirox nanoparticles on human breast cancer cells (SKBR3) and mouse breast cancer cells (4T1) compared with the drug form.
Materials and methods: Deferasirox nanoparticles were synthesized by Poly lactic-co-glycolic acid (PLGA) moiety with emulsion formation and solvent evaporation. Cytotoxicity was evaluated using the MTT assay and their 50% inhibitory concentration (IC50) were assessed in SKBR3 and 4T1.
Results: Findings showed that IC50 of nano-deferasirox for SKBR3 and 4T1 were 9.09±0.011 µg/ml and 6.6±0.032 µg/ml, respectively and the IC50 of the deferasirox drug form for SKBR3 and 4T1 IC50 were 21.07±0.003 µg/ml and 11.08±0.013 µg/ml, respectively.
Conclusion: The anticancer effects of deferasirox were confirmed on the cell lines, and the improved properties and efficacy were also confirmed on two cancer cell lines. Nanoparticle delivery systems improve absorption and drug properties and increase the effectiveness of the drug.

 

---

 Background and purpose: Lead poisoning induces oxidative stress and causes disorders in several organs. Iron-chelating drugs can form a complex with toxic metals such as lead and lower their content in the blood and tissues. This study aims to examine the antioxidant effects of Deferasirox, Deferiprone, and their combination in rats with subchronic lead exposure.
Materials and methods: In this interventional study, lead poisoning was induced in Sprague-Dawley male rats by gavage administration of 30 mg/kg lead acetate for 60 days. The animals were treated with Deferasirox (140 mg/kg), Deferiprone (300 mg/kg), and their combination through oral gavage from days 47 to 60 of the experiment (14 days). Lead concentration was measured by flame atomic absorption spectroscopy. We examined malondialdehyde (MDA) level, nitric oxide metabolites (NOx) as nitro-oxidative stress markers, glutathione (GSH), and total antioxidant capacity (TAC) in the blood, brain, liver, kidney, and testis. Data analysis was performed in Graphpad Prism software applying one-way variance analysis and Tukey's test.
Results: Lead poisoning increased the concentration of this metal and nitro-oxidative stress and decreased the TAC and GSH in the brain, liver, kidney, and testis (P<0.05). Alone or in combination, Defropyrone and Defrasirox lowered the lead content in the blood and tissues of rats. In addition, treatment with these two chelators resulted in drops in MDA and NOx levels and increase in TAC and GSH levels (P<0.05), although these effects were most pronounced when the medicines were administered together.
Conclusion: In addition to their antioxidant properties, it seems that Defropyrone and Defrasirox have synergistic effects in lowering lead content in blood and other tissues.