Pharmacokinetics of Deferiprone in Patients with β-Thalassaemia

Limenta, Lie Michael George; Jirasomprasert, Totsapol; Jittangprasert, Piyada; Wilairat, Prapin; P, Yamanont; Chantharaksri, Udom; Fucharoen, Suthat; Morales, Noppawan Phumala

doi:10.2165/11536630-000000000-00000

Cited by 16 publications

(25 citation statements)

References 30 publications

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“…Our previous study demonstrated that the pathophysiology of patients, including iron status and splenectomy, influenced pharmacokinetics and UIE [13]. Genetic polymorphism of the drug-metabolizing enzyme (UGT1A6) did not play a significant role in the variation [14].…”

Section: Comparison Of Pharmacokinetics and Urinary Ironmentioning

confidence: 87%

“…Glucuronide Methods of analysis were described in our previous report [13,14]. Briefly, serum samples were deproteinized by ultrafiltration with Amicon Centrifree® micropartition devices (Millipore Corp., Bedford, Mass., USA).…”

Section: Quantitative Analysis Of Deferiprone and Deferipronementioning

confidence: 99%

“…The absorbance of the Fe 2+ -BPT complex was measured at 537 nm with a UV-visible spectrophotometer (Cintra 10e, GBC, Melbourne, Vic., Australia). Deferipronechelated iron (DCI) was calculated from the area under the curve of the NTBI serum profile as previously described [13].…”

Section: Determination Of Iron Profile Deferiprone-chelated Iron Andmentioning

confidence: 99%

“…A terminal disposition rate constant was calculated by linear least-squares regression of the log-transformed serum concentration-time data. The terminal elimination half-life (elt 1/2 ), area under concentration time curve from time zero to infinity (AUC 0-∞ ), apparent clearance (CL/F) and volume of distribution (Vd/F) were calculated as described in a previous report [13,14].…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

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Comparison of Pharmacokinetics and Urinary Iron Excretion of Two Single Doses of Deferiprone in ß-Thalassemia/Hemoglobin E Patients

et al. 2012

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Section: Comparison Of Pharmacokinetics and Urinary Ironmentioning

confidence: 87%

Section: Quantitative Analysis Of Deferiprone and Deferipronementioning

confidence: 99%

Section: Determination Of Iron Profile Deferiprone-chelated Iron Andmentioning

confidence: 99%

Section: Pharmacokinetic Analysismentioning

confidence: 99%

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Comparison of Pharmacokinetics and Urinary Iron Excretion of Two Single Doses of Deferiprone in ß-Thalassemia/Hemoglobin E Patients

et al. 2012

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“…The program has started in 2001 from synthesizing compound from raw material, testing the product for all international chemical and biochemical standard, evaluating bioequivalence with original product to finally determining pharmacokinetic profiles in healthy volunteers and thalassemia patients [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

et al. 2013

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Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy-three pediatric patients with severe b thalassemias, age range 3.2-19 years, were recruited to a 1-year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty-four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.164.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml 21 . Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml 21 had the most significant fall of SF at 1 year. A subgroup analysis by MRI-T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug-related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles. Am. J. Hematol. 88:251-260,

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Randomized, Blinded, Placebo‐ and Positive‐Controlled Crossover Study to Determine the Effect of Deferiprone on the QTc Interval in Healthy Subjects

Fradette¹,

Rozova²,

Stilman³

et al. 2017

Clinical Pharm in Drug Dev

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This study evaluated whether deferiprone, an oral iron chelator, acts to prolong the QT interval. Fifty healthy volunteers received single doses of each of the following: therapeutic dose of deferiprone (33 mg/kg), supratherapeutic dose (50 mg/kg), placebo, or moxifloxacin, a positive control known to significantly prolong QT interval. Following each dose, subjects underwent cardiac monitoring, pharmacokinetics assessments, and safety assessments. Based on the QT interval obtained using the Fridericia correction for heart rate (QTcF), the upper bound of the 1-sided 95% confidence interval of the mean difference between deferiprone and placebo was <10 milliseconds (the threshold of concern defined by authorities) at all time points for both doses: maximum difference of 3.01 milliseconds for the therapeutic dose and 5.23 milliseconds for the supratherapeutic dose. The difference in dQTcF between moxifloxacin and placebo demonstrated that the study was adequately sensitive to detect a significant prolongation of QTcF. The concentration-response correlation analyses revealed some weak but statistically significant trends of increase in dQTcF and ddQTcF with increasing exposure to deferiprone, but these trends should have no clinical consequence even at the recommended maximum dosage. In conclusion, there was no clinically meaningful effect on QTc interval following single therapeutic or supratherapeutic doses of deferiprone.

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Pharmacokinetics of Deferiprone in Patients with β-Thalassaemia

Cited by 16 publications

References 30 publications

Comparison of Pharmacokinetics and Urinary Iron Excretion of Two Single Doses of Deferiprone in ß-Thalassemia/Hemoglobin E Patients

Comparison of Pharmacokinetics and Urinary Iron Excretion of Two Single Doses of Deferiprone in ß-Thalassemia/Hemoglobin E Patients

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Randomized, Blinded, Placebo‐ and Positive‐Controlled Crossover Study to Determine the Effect of Deferiprone on the QTc Interval in Healthy Subjects

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Pharmacokinetics of Deferiprone in Patients with β-Thalassaemia

Cited by 16 publications

References 30 publications

Comparison of Pharmacokinetics and Urinary Iron Excretion of Two Single Doses of Deferiprone in ß-Thalassemia/Hemoglobin E Patients

Comparison of Pharmacokinetics and Urinary Iron Excretion of Two Single Doses of Deferiprone in ß-Thalassemia/Hemoglobin E Patients

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Randomized, Blinded, Placebo‐ and Positive‐Controlled Crossover Study to Determine the Effect of Deferiprone on the QTc Interval in Healthy Subjects

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Product

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About

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand