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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalTherapeutic Drug Monitoring
DOIs
Publication statusAccepted/In press - Jan 30 2017

Fingerprint

beta-Thalassemia
Iron
Ferritins
alanylglycine
Serum
Norleucine
Chelation Therapy
deferasirox
Amino Acids
Thalassemia
Drug Monitoring
Pharmaceutical Preparations
Serine
Arginine
Liver

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Deferasirox-Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in β-Thalassemia Major. / Lu, Meng Yao; Lin, Ting Hao; Chiang, Po Hung; Kuo, Pei Hsin; Wang, Ning; Wu, Wen Hsin; Lin, Kai Hsin; Wu, Tzu Hua.

In: Therapeutic Drug Monitoring, 30.01.2017.

Research output: Contribution to journalArticle

Lu, Meng Yao ; Lin, Ting Hao ; Chiang, Po Hung ; Kuo, Pei Hsin ; Wang, Ning ; Wu, Wen Hsin ; Lin, Kai Hsin ; Wu, Tzu Hua. / Deferasirox-Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in β-Thalassemia Major. In: Therapeutic Drug Monitoring. 2017.
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abstract = "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.",
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T1 - Deferasirox-Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in β-Thalassemia Major

AU - Lu, Meng Yao

AU - Lin, Ting Hao

AU - Chiang, Po Hung

AU - Kuo, Pei Hsin

AU - Wang, Ning

AU - Wu, Wen Hsin

AU - Lin, Kai Hsin

AU - Wu, Tzu Hua

PY - 2017/1/30

Y1 - 2017/1/30

N2 - 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.

AB - 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.

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