Although successful iron chelation with deferiprone is associated with significant complications, patient’s compliance with medication regimens is of a high priority. The present study did evaluate the complications and compliance of domestically- manufactured deferiprone combined with desferrioxamine for iron chelation therapy. A total of 32 major beta thalassemic patients with cardiomyopathy were enrolled in the study and were monitored clinically and paraclinically. Upon every visit, the patients were prescribed only the number of tablets deemed necessary. The side effects observed as nausea (25%), vomiting (12%), neutropenia (12%), thrombocytopenia (6%), and joint pain (3%) without agranulocytosis or increased liver enzymes to more than twice the normal values. Deferiprone was discontinued in 30% of patients because of severe refractory gastrointestinal complaints (12%), recurrent neutropenia (6%), recurrent thrombocytopenia (6%), severe arthropathy (3%), or interferon therapy (3%). None of the patients, except one, remembered taking full number of the prescribed tablets. Twenty seven patients used 35% to 92% of the prescribed tablets. Poor compliance with deferiprone due to patient’s neglect to take the drug 3 times a day for a prolonged period was the main problem in this regimen. Although thrombocytopenia was more common compared with those of previous reports, other complications were seen with equal or lower frequencies.This study shows that a lower daily dose is the most favorable property of an oral iron chelator for prolonged usage.

Background and Objectives Iron overload especially in heart is one of the most important causes of death among patients with major thalassemia. Chelation therapy is one of the main therapeutic methods in these patients. This study was done to compare the therapeutic effects of deferoxamine (DFO) and deferiprone combination therapy with deferoxamine alone in the patients of Mazandaran, Iran.Materials and Methods In this clinical trial, major thalassemia patients with serum ferritin>3000 ng/ml were divided into two groups and matched based on age, sex, serum ferritin levels and cardiac systolic function (LVEF). First group received DFO alone and second group received combination therapy of deferiprone and deferoxamine. The patients were physically examined every month; serum ferritin, mean Hb, AST, ALT, and LVEF also started to be measured 6 months prior to the study and subsequently at every visit. Data were analyzed using t-test and X² test.Results There were fifty patients in each group in single and combination therapy groups. Duration of F/U was 28.5 ± 6.2 months. Serum ferritin levels in single and combination therapy groups were 4100 ± 1400 and 4500 ± 1700 ng/ml during 6 months before the study, respectively; the levels decreased to 4600 ± 2200 and 3800 ± 1400 ng/ml at the end of treatment, respectively (p<0.05). Only 3 patients had leukopenia and 10 had nausea in combination therapy group.Conclusions The study showed that the combination therapy has a better effect on decreasing the serum level ferritin. Moreover, it can improve LVEF.

A sensitive fluorometric method for the determination of deferiprone (DFP) based on the formation of a luminescent complex with Tb3+ions in aqueous solutions is reported. The maximum excitation and emission wavelengths were 295 and 545 nm, respectively. The effects of various factors on the luminescence intensity of the system were investigated and optimized, then under the optimum conditions, the method was validated. The method validation results indicated that the relative intensity at 545 nm has a linear relationship with the concentration of DFP in aqueous solutions at the range of 7.2×10-9 to 1.4×10-5 M, the detection and quantification limits were calculated respectively as 6.3×10-9 and 2.1×10-8 M, precision and accuracy of the method were lower than 5% and the recovery was between 100.1% and 102.3%. The results indicated that this method was simple, time saving, specific, accurate and precise for the determination of DFP in aqueous solutions. After optimization and validation, the method successfully applied for determination of DFP in tablet dosage forms. The stoichiometry of the Tb3+-DFP complex was found as 1: 3 and the complex formation constant was 1.6×1016.

Background and Objective: Deferoxamin is the current “gold standard” chelator in comparison with new chelators. Combined therapy of Deferiprone and deferoxamin reduces the cardiac iron overload in patients with major talassemia. This study was done to evaluate the effect of defriprone-deferoxamine on heart function in patients with major thalassemia.Methods: In this historical cohort study, 8 patients with major beta thalassemia treated by subcutaneous deferoxamine were randomly selected and LVEF (the rate of blood that exited from heart in each beat) and serum ferritin were measeared. The patients were treated by deferiprone (50-100 mg/kg/day) compained with dferoxamine (30-50 mg/kg as 3 times in a week). In the end of each year, LVEF and serum ferritin of patients were measured.Results: The ferritin level changed from 3243.12 in the first year to 2672.75 mg/kg at the end of third year. The mean of LVEF changed from 71.12% to 64.62 %. The correlation of serum ferritin and LVEF only at the end of third year was significant (P<0.05).Conclusion: Combined therapy of deferiprone-deferoxamine during 3 years reduces ferritin and LVEF in patients with major thalassemia.

In the current study, the solubility and density of deferiprone were determined in the polyethylene glycol (PEG) 400 and 2-propanol mixtures at 293.2 – 313.2 K using a shake-flask method before a spectrophotometric method. The results showed that the solubility increases with both PEG 400 mass fraction and temperature increase. The measured data were fitted to some mathematical models including van’t Hoff, MRS, Jouyban-Acree, Jouyban-Acree–van’t Hoff, and the modified Wilson models. The results from the investigation of model accuracy showed that there were only tiny differences between measured data and back-calculated data from solubility values (MRD% <3.5%). Moreover, thermodynamic studies showed that the deferiprone dissolution process was endothermic and entropy-driven, and the main contributor of ΔG° was the enthalpy

In the current study, the solubility and density of deferiprone were determined in the polyethylene glycol (PEG) 400 and 2-propanol mixtures at 293.2 – 313.2 K using a shake-flask method before a spectrophotometric method. The results showed that the solubility increases with both PEG 400 mass fraction and temperature increase. The measured data were fitted to some mathematical models including van’t Hoff, MRS, Jouyban-Acree, Jouyban-Acree–van’t Hoff, and the modified Wilson models. The results from the investigation of model accuracy showed that there were only tiny differences between measured data and back-calculated data from solubility values (MRD% <3.5%). Moreover, thermodynamic studies showed that the deferiprone dissolution process was endothermic and entropy-driven, and the main contributor of ΔG° was the enthalpy

Background: Cardiac complications due to iron overload are the most common causes of death in patients with major thalassemia. This study assessed the efficacy of iron chelating by desferal-L1 in improvement of cardiac function in patients with major thalassemia. Methods and Materials: Patients older than 8 years old with major thalassemia that were admitted to hematology ward of Ali-e-Asghar hospital of Zahedan in 2005-2006 and had lower than normal diastolic indices in annual echocardiography were considered as study population. During primary tests, indices of diastolic function of left and right hearts were calculated, using echocardiography with 2D, M-mode and Doppler then the patients were placed on a combination of desferal (30- 40mg/kg/day two nights per week) and L1 (deferiprone) (75mg/kg/day, three times a day). At the end of the study, cardiac indices were calculated again. Data were using SPSS software and paired t-test and P<0.05 was considered as significant level. Results: Of 38 patients, who were treated with a combination of desferal-L1, 19 were female with the mean age of 16.9±3.1 and 18 were male with the mean age of 17.3±2.6 years. Diastolic indices of right ventricle had no significant difference before and after treatment except PET/ET which decreased significantly after treatment (P<0.05). Of diastolic indices of left ventricule peak-Evelocity and IVRT and E/A ratio decreased significantly after treatment (P<0.05). The difference of peak-A-velocity before and after treatment was not significant (P>0.05). Systolic indices of left ventricule increased significantly after treatment (P<0.05).Conclusion: In this study, after one year of treatment with a combination of desferal-L1 in patients with major thalassemia, echocardiography showed improvement in left heart systolic and diastolic function. This combination therapy prevented progression of right ventricular diastolic function abnormality.