In:
Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 39, No. 2 ( 2017-04), p. 185-191
Abstract:
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 (C trough ) and 2 hours postdose (C 2h ) were determined. Because 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 postdose. Results: A total of 28 patients either dosing daily or twice daily were recruited. After a 1-month DEFR maintenance therapy, 38.8% and 30% of patients from groups of once-daily and twice-daily, respectively, had a plasma DEFR–iron complex formation ratio higher than 0.05 [High Chelation Ratio, (HCR)]. After a 6-month follow-up, those patients who had a HCR (n = 10) at C 2h 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; n = 18; +10.5; +4.5) compared with the baseline. The levels of plasma l -arginine, l -alanine, l -glycine, l -norleucine, and l -serine were significantly lower in patients with the low Chelation Ratio condition than the levels in HCR patients. Conclusions: This therapeutic drug monitoring study revealed that a DEFR–iron complex formation ratio at C 2h 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 need to be validated in a larger cohort.
Type of Medium:
Online Resource
ISSN:
0163-4356
DOI:
10.1097/FTD.0000000000000378
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2048919-5
SSG:
15,3
