جستجوی مقالات مرتبط با کلیدواژه « دفریپرون » در نشریات گروه « پزشکی »

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.

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.

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.

In addition to their antioxidant properties, it seems that Defropyrone and Defrasirox have synergistic effects in lowering lead content in blood and other tissues.

Thalassemia syndromes are the most common inherited hemoglobinopathies in the world characterized by various degrees of defective production of the alpha or beta globin chains. Impairment in alpha chain or beta chain synthesis leads to alpha thalassemia and beta thalassemia syndromes respectively.
Iran is one of the countries located on the thalassemia belt therefore this disease is significant in our country. The most important component of treatment in beta thalassemia is packed red blood cell transfusion. Thalassemic patients need lifelong transfusions and the consequence of these repeated transfusions is iron accumulation in different organs, such as heart, liver and endocrine gland. Iron overload is one of the major causes of morbidity in patients with thalassemia major necessitating iron chelation drugs to improve survival of patients. Three iron chelating agents are currently commercially available: deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX). DFO is the first chelating agent that became available. DFP is the first oral iron chelator and DFX is the most recently approved chelator for transfusional hemosiderosis. The purpose of this article is to summarize the main pharmacokinetic characteristics and side effects of iron chelator drugs in the field of thalassemia.

Selection of iron chelator medication for thalassemic patients depends on clinical and laboratory characteristics such as age, serum ferritin and severity of different organ damage. Patient choice is also important because the compliance to treatment is essential. Policy makers should decide to import brands versus to facilitate making medicationsin the country. Insurance companies also should decide for coverage the costs. In this paper we report the current situation of iron chelator usage for patients with beta thalassemia major in our center.
We reviewed data the medical records of patients in November 2015.
There were 463 patients on iron chelator medications. Three hundred and thirty patients (71.2%) had regular blood transfusions and reminders were not on regular blood transfusion. Two hundred and fifty one (54%), and 212(46%) were using one or two iron chelators, respectively. Two hundred and two (44%) patients were using a combination of a parenteral and one oral medication. Sixty seven (14%) patients were using only parenteral iron chelator. The most common used medication was Osveral (made in Iran by Osveh Pharmaceutical) in about one third of patients. All non-transfusion dependent patients were using Osveral. The parenteral medication (Desferrioxamine) was distributed in two brands. One imported brand as Desferal (Novartis) and the other as Desfonak (made in Iran by Ronak Daru).Deferiprone(made in Avesina, Iran) was used in combination with desferrioxamine in 141 patients and as the only treatment in 11 patients.
Availability of different types of medications makes the opportunity to select the best protocol for patients.

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. 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. 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). Combined therapy of deferiprone-deferoxamine during 3 years reduces ferritin and LVEF in patients with major thalassemia.

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 χ² 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.

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 then 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.

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-E-velocity and IVRT and E/A ratio decreased significantly after treatment (p <0.05). t he 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).

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.

Regular blood transfusions in beta thalassemic patients can lead to accumulation of extra iron in the body which may result in cardiac complications and death. Deferrioxamin (DFO) is the standard treatment for this condition but 12-8 hours subcutaneous (SQ) injection of this drug per day can cause local pain which together with lack of patients´ compliance, it is necessary to use another drug to improve the condition of the patients. Deferiprone (DFP), is an approved drug for this purpose and removes iron from cells including cardiac muscle cells. The aim of this study is to compare efficacy of deferrioxamin with that of combined deferiprone and deferrioxamin on echocardiographic indices in beta thalassemic patients. In this randomized clinical trial 40 thalassemic patients who met the inclusion criteria of this study were divided into two equal groups. Controls group received SQ deferrioxamin for six days/week and intervention group received deferrioxamin for three days/week and deferiprone orally for four days/week. Cardiac indices were measured and compared before and after the study. Mean values of the age of the patients were 15.6±5.1 and 14.1±6 years in the intervention and control group respectively. Right ventricle diameter (RVD) indices in control group was 18.7±7.6 and 20.8±6.6 mm before and after treatment respectively (P<0.05). In the intervention group RVD indices were 19.5±5.8 and 18.0 ±4.7 mm before and after treatment respectively (P>0.05). Other indices such as LVEDD, LVESD, aortic root diameter, EF and Fs of left ventricle and also indices of the heart valves revealed no significant differences between the two groups. We didn’t observe any side effect of the drugs in the patients. We concluded combined therapy with 4 days DFP and 3 days DFO per week did not lead to cardiac complications and deterioration of echocardiographic indices.

Background and Cardiac complications in major thalassemia are the most debilitating problem among them. Iron chelating with desferrioxamine, may be difficult or inadequate. The aim of this research is to evaluate the effect of combination therapy with the two drugs "deferiprone & desferrioxamine" on cardiac complications in major thalassemia. In a clinical trial study (before & after), 47(24men and 23 women) patients with major thalassemia referred to Booali research center,10 to 35 years old, all of whom were undertaken combination therapy with deferiprone & desferrioxamine, enrolled in this study. Echocardiography was performed for all patients before & after at least 6 months of combination therapy. Echocardiographic systolic & diastolic function indices including LVEF, EPSS, CI&E/A, EF slope & MPI, as well as presence of arrhythmia were obtained. The data were analyzed by paired T Test & Pearson correlation. There were significant changes in ferritin, systolic function& MPI, indicating statistically significant improvement. Ferritin decreased to 3306±1347ng/ml from 4489±1607ng/ml (p=0.000). LVEF increased to 69.7±2.6% from 67.6±3.9% (p=0.04). EPSS decreased to 2.9±1.3mm from 3.9±2.1mm (p=0.004). Cardiac Index increased to 3.6±0.18 from 3.5±0.3 (p=0.02). MPI decreased to 0.33±0.05 from 0.37±0.06 (p=0.03). Arrhythmia & diastolic function were also slightly improved which were statistically nonsignificant. The results showed that combination therapy with the two drugs deferiprone & desferrioxamine led to decrease ferritin level and improve systolic function in patients with major thalassemia.