Deferasirox-iron complex formation ratio as an indicator of long-term chelation efficacy in β-thalassemia major

Meng Yao Lu, Ting Hao Lin, Po Hung Chiang, Pei Hsin Kuo, Ning Wang, Wen Hsin Wu, Kai Hsin Lin, Tzu Hua Wu

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

BACKGROUND:: β-Thalassemia major patients with higher total drug levels (deferasirox [DEFR] plus its iron complex) do not yield better serum ferritin (SF) control. This study aimed to determine the concentrations of DEFR and its iron complex (Fe-[DEFR]2) in thalassemia patients to predict the chelation efficacy in terms of SF and cardiac T2* values. METHODS:: Patients’ steady-state drug levels at trough (Ctrough) and 2 hours post-dose (C2h) were determined. Since iron deposition may cause changes in the hepatic metabolism of amino acids, the concentrations of 40 amino acids in plasma were also assayed at 2 hours post-dose. RESULTS:: A total of 28 patients either dosing daily (QD) or twice daily (BID) were recruited. After one-month DEFR maintenance therapy, 38.8% and 30% patients from groups of QD and BID, respectively, had a plasma DEFR-iron complex formation ratio higher than 0.05 (High Chelation Ratio, HCR). After a six-month follow-up, those patients who had a HCR (n = 10) at C2h showed more favorable median changes in SF and cardiac T2* values (−388.0, +10.1) than those with a low DEFR-iron complex formation ratio (Low Chelation Ratio, LCR; n = 18; +10.5; +4.5) compared to the baseline. The levels of plasma L-arginine, L-alanine, L-glycine, L-norleucine, and L-serine were significantly lower in patients with the LCR condition than the levels in HCR patients. CONCLUSIONS:: This therapeutic drug monitoring study revealed that a DEFR-iron complex formation ratio at C2h might be an applicable indicator of the efficacy of long-term DEFR iron chelation therapy. A better iron-control response to DEFR was observed in the patients with HCRs. The trends for the ratio might have value in dose-setting and needs to be validated in a larger cohort.
原文英語
頁(從 - 到)185-191
頁數7
期刊Therapeutic Drug Monitoring
39
發行號2
DOIs
出版狀態已發佈 - 2017

ASJC Scopus subject areas

  • 藥學(醫學)
  • 藥理

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