The pharmacokinetics and blood-brain barrier permeation of the chelators 1,2 dimethyl-, 1,2 diethyl-, and 1-[ethan-1′ ol]-2-methyl-3-hydroxypyridin-4-one in the rat

Fredenburg, Andrea M.; Sethi, Rajiv K.; Allen, David; Yokel, Robert A.

doi:10.1016/0300-483x(95)03301-u

Cited by 91 publications

(73 citation statements)

References 21 publications

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“…Deferiprone is unique among iron chelators in that it crosses the blood-brain barrier to chelate iron in the central nervous system. 4 This case report provides proof of concept because the MR imaging confirms a reduction in hemosiderin deposition in the brain. Most important, the reduction in hemosiderin deposition correlates with neurologic improvement, suggesting that superficial siderosis is a reversible condition once the iron products are removed from the nervous system.…”

Section: Discussionsupporting

confidence: 53%

“…We proposed a trial of deferiprone, a lipid-soluble iron chelator, which has been shown to easily cross the blood-brain barrier and chelate iron in the central nervous system of animals. 4 A trial dose of deferiprone at 30 mg/kg/day was started in January 2008 and was followed with weekly blood counts and monthly assessment of ferritin levels. Due to perceived adverse effects of joint and muscle aches and a low ferritin level, the dose was decreased to 15 mg/kg/day in July 2008.…”

Section: Case Reportmentioning

confidence: 99%

“…Deferiprone (L1) is a lipid-permeable iron chelator that has been used for treatment of thalassemias and other iron metabolism disorders since 1989. 3,4 We report on a patient with superficial siderosis who was treated with deferiprone for 1.5 years. We found a remarkable reduction in hemosiderin on MR imaging of the brain, associated with clinical improvement in symptoms.…”

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confidence: 99%

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Deferiprone Reduces Hemosiderin Deposits in the Brain of a Patient with Superficial Siderosis: Fig 1.

Lévy¹,

Llinás²

2010

AJNR Am J Neuroradiol

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Section: Discussionsupporting

confidence: 53%

Section: Case Reportmentioning

confidence: 99%

mentioning

confidence: 99%

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Deferiprone Reduces Hemosiderin Deposits in the Brain of a Patient with Superficial Siderosis: Fig 1.

Lévy¹,

Llinás²

2010

AJNR Am J Neuroradiol

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“…5 Therefore, it may penetrate the blood ocular barrier and deliver a considerable level to the aqueous humour, just as it penetrates the blood brain barrier. 8 There, it could decrease the activity of the enzyme glutathione peroxidase, which subsequently may cause lenticular opacities. 9,10 In addition, the deferiprone-iron complex may ultrafiltrate through the thinner posterior capsule and deposit in the adjacent cortex.…”

Section: Discussionmentioning

confidence: 99%

Posterior subcapsular opacity in two patients with thalassaemia major following deferiprone consumption

Mehdizadeh

Nowroozzadeh

2009

Clinical and Experimental Optometry

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“…Deferiprone has physicochemical characteristics (low molecular weight, favorable octanol:water partition coefficient, neutral charge) that allow good permeability of mitochondrial walls and the blood-brain barrier. 9,10 In addition, in the setting of regional iron overload, it seems that deferiprone has iron-relocating and redistributing abilities enabling it to act as a reverse siderophore. 10,11 Deferiprone (30 mg/kg/day) was used in 9 patients with Friedreich's ataxia (FA), evaluated using the International Cooperative Ataxia Rating Scale (ICARS) and brain MRI.…”

Section: Introductionmentioning

confidence: 99%

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation

Abbruzzese¹,

Cossu²,

Balocco³

et al. 2011

Haematologica

122

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Acknowledgments: this is a not-for-profit study. We thank Jane Tricker and Silvia Caviglia for editorial assistance in the preparation of this article. We are also grateful to Alessandra Rosa for assistance with the statistical analysis. This trial was partially supported by E.O. Ospedali Galliera Scientific Committee and Fondazione CARIGE. Manuscript received on February 24, 2011. Revised version arrived on June 30, 2011. Manuscript accepted on July 4, 2011. Email: gianluca.forni@galliera.it Deferiprone was shown to reverse iron deposition in Friedreich's ataxia. This multi-center, unblinded, single-arm pilot study evaluated safety and efficacy of deferiprone for reducing cerebral iron accumulation in neurodegeneration with brain iron accumulation. Four patients with genetically-confirmed pantothenate kinase-associated neurodegeneration, and 2 with parkinsonism and focal dystonia, but inconclusive genetic tests, received 15 mg/kg deferiprone bid. Magnetic resonance imaging and neurological examinations were conducted at baseline, six and 12 months. Chelation treatment caused no apparent hematologic or neurological side effects. Magnetic resonance imaging revealed decreased iron accumulation in the globus pallidus of 2 patients (one with pantothenate kinase-associated neurodegeneration). Clinical rating scales and blinded video rating evaluations documented mild-to-moderate motor improvement in 3 patients (2 with pantothenate kinaseassociated neurodegeneration). These results underline the safety and tolerability of deferiprone, and suggest that chelating treatment might be effective in improving neurological manifestations associated with iron accumulation. Haematologica 2011;96(11):1708-1711. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACTly, agranulocytosis), currently represents the only possibility for removing and/or preventing iron accumulation in the brain. This was a multi-center, unblinded, single-arm pilot study, lasting one year, to evaluate the efficacy and safety of chelation therapy with deferiprone on cerebral iron accumulation in patients with a clinical diagnosis of NBIA. 4 Design and Methods PatientsInclusion criteria were: patients over 18 years of age with neurological symptoms correlated with iron deposition in the basal ganglia as documented by MRI (T2* and T2 signal decrease in the basal ganglia), performed within six months of enrolment. Exclusion criteria were: inability to undergo MRI; renal insufficiency (creatinine >1.5 mg/dL); neoplasias, systemic cardiovascular, severe renal and hepatic diseases; known hypersensitivity to deferiprone; pregnancy and breastfeeding. Additional exclusion criteria were average alanine transaminase (ALT) levels over 300, variations in ALT or aspartate transaminase (AST) levels of 300% during the year prior to enrolment, and patients judged potentially unreliable and/or uncooperative with regard to study procedures.The trial was approved by the E.O. Ospedali Galliera Ethics Committee and the local Ethics Committee at the Cagliari cent...

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The pharmacokinetics and blood-brain barrier permeation of the chelators 1,2 dimethyl-, 1,2 diethyl-, and 1-[ethan-1′ ol]-2-methyl-3-hydroxypyridin-4-one in the rat

Cited by 91 publications

References 21 publications

Deferiprone Reduces Hemosiderin Deposits in the Brain of a Patient with Superficial Siderosis: Fig 1.

Deferiprone Reduces Hemosiderin Deposits in the Brain of a Patient with Superficial Siderosis: Fig 1.

Posterior subcapsular opacity in two patients with thalassaemia major following deferiprone consumption

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation

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