Publication:
Pharmacokinetics of deferiprone in patients with β-thalassaemia: Impact of splenectomy and iron status

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Issued Date

2011

Resource Type

Article

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application/pdf

ISSN

3125963

DOI

10.2165/11536630-000000000-00000

Other identifier(s)

2-s2.0-78649929842

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

Clinical Pharmacokinetics. Vol 50, No.1 (2011), p.41-50

Suggested Citation

Limenta L.M.G., Jirasomprasert T., Jittangprasert P., Wilairat P., Yamanont P., Chantharaksri U., Fucharoen S., Morales N.P. Pharmacokinetics of deferiprone in patients with β-thalassaemia: Impact of splenectomy and iron status. Clinical Pharmacokinetics. Vol 50, No.1 (2011), p.41-50. doi:10.2165/11536630-000000000-00000 Retrieved from: https://hdl.handle.net/20.500.14740/7432

Title

Pharmacokinetics of deferiprone in patients with β-thalassaemia: Impact of splenectomy and iron status

Author(s)

Limenta L.M.G.
 Jirasomprasert T.
 Jittangprasert P.
 Wilairat P.
 Yamanont P.
 Chantharaksri U.
 Fucharoen S.
 Morales N.P.

Abstract

Background and Objective: Iron-rich transfusions and/or a compensatory increase in iron absorption ultimately result in iron loading in patients with b-thalassaemia. Hence, without iron chelation, iron accumulates relentlessly. Deferiprone has been shown to be capable of reducing the iron burden in patients with b-thalassaemia. However, there is wide interpatient variation in deferiprone-induced urinary iron excretion (UIE). We hypothesized that splenectomy and iron status might influence the pharmacokinetic profiles of deferiprone in patients with b-thalassaemia/haemoglobin E, and the present study was aimed at examining this hypothesis. Study Participants and Methods: Thirty-one patients with b-thalassaemia/haemoglobin E (20 splenectomized and 11 non-splenectomized patients) were enrolled in the study. After an overnight fast, the subjects received a single oral dose of deferiprone 25mg/kg of bodyweight. Blood samples were collected pre-dosing and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 and 480 minutes after dosing. Urine output was pooled and collected at 0-2, 2-4, 4-8, 8-12 and 12-24 hour intervals. Serum and urine concentrations of deferiprone and its metabolite deferiprone glucuronide were determined using a validated high-performance liquid chromatography method. Serum deferiprone-chelated iron and UIE were determined using a validated colourimetric method. Results: No significant difference in the pharmacokinetic parameters of non-conjugated deferiprone was observed between splenectomized and non-splenectomized patients. However, the maximum serum concentration (C max) and the area under the serum concentration-time curve (AUC) from time zero to infinity (AUC 1 ) values of deferiprone glucuronide were significantly lower (both p < 0.05) in splenectomized patients (median 53.2 μmol/L and 12 634 μmol • min/L, respectively) than in non-splenectomized patients (median 70.5 μmol/L and 20 601 mmol • min/L, respectively). The Cmax and the AUCfrom time zero to the time of the last measurable concentration (AUClast) values of serum deferiprone-chelated iron, as well as UIE, were significantly higher (p < 0.001) in splenectomized patients (median values 7.1 μmol/L, 1645 μmol • min/L and 77.1 μmol, respectively) than in non-splenectomized patients (median values 3.1 μmol/L, 545 μmol • min/L and 12.5 μmol, respectively). Urinary excretion of non-conjugated deferiprone and deferiprone glucuronide did not differ between the two groups. Further analyses using multiple linear regressions indicated that the iron profiles (non-transferrin-bound iron and ferritin) were significant predictors of the pharmacokinetic parameters of non-conjugated deferiprone, deferiprone-chelated iron and UIE. In addition, splenectomy status was identified as the strongest predictor of the AUClast of deferiprone-chelated iron and UIE. Conclusion: Both iron and splenectomy status have significant effects on the pharmacokinetics and iron chelation efficacy of deferiprone. A greater degree of iron overload in splenectomized patients results in alterations in pharmacokinetic parameters (theCmax and AUC) of deferiprone glucuronide and deferipronechelated iron, as well as a significant increase in UIE. © 2011 Adis Data Information BV. All rights reserved.

Subject(s)

Deferiprone
 Deferiprone glucuronide
 Drug metabolite
 Ferritin
 Gpo l1
 Hemoglobin E
 Iron
 Iron chelate
 Transferrin
 Unclassified drug
 Adult
 Area under the curve
 Article
 Beta thalassemia
 Blood sampling
 Diet restriction
 Drug activity
 Drug blood level
 Drug conjugation
 Drug efficacy
 Drug urine level
 Female
 Glucuronidation
 High performance liquid chromatography
 Human
 Iron binding capacity
 Iron blood level
 Iron chelation
 Iron metabolism
 Iron overload
 Maximum plasma concentration
 Multiple linear regression analysis
 Plasma concentration-time curve
 Priority journal
 Single drug dose
 Splenectomy
 Urinary excretion
 Urine volume
 Administration, Oral
 Adult
 Area Under Curve
 Beta-Thalassemia
 Blood Transfusion
 Female
 Ferritins
 Hemoglobin E
 Humans
 Iron
 Iron Chelating Agents
 Iron Overload
 Male
 Pyridones
 Splenectomy
 Transferrin

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https://hdl.handle.net/20.500.14740/7432

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