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.
ASJC Scopus subject areas
- Pharmacology (medical)
Lu, M. Y., Lin, T. H., Chiang, P. H., Kuo, P. H., Wang, N., Wu, W. H., Lin, K. H., & Wu, T. H. (認可的出版社/出版中). Deferasirox-Iron Complex Formation Ratio as an Indicator of Long-term Chelation Efficacy in β-Thalassemia Major. Therapeutic Drug Monitoring. https://doi.org/10.1097/FTD.0000000000000378