Simultaneous Determination of Plasma Deferasirox and Deferasirox-Iron Complex Using an HPLC-UV System and Pharmacokinetics of Deferasirox in Patients with β-Thalassemia Major: Once-daily Versus Twice-daily Administration

Meng Yao Lu, Ning Wang, Wen Hsin Wu, Cheng Wei Lai, Pei Hsin Kuo, Po Hung Chiang, Kai Hsin Lin, Tzu Hua Wu

研究成果: 雜誌貢獻文章同行評審

16 引文 斯高帕斯(Scopus)

摘要

Purpose Deferasirox (DEFR), when administered BID, improves iron overload and decreases DEFR-related adverse effects in patients with β-thalassemia major. However, the pharmacokinetic (PK) disposition of DEFR and the iron-DEFR complex (Fe-[DEFR]2) in this dosing strategy is unclear. Methods Chromatographic analysis was performed using a solvent delivery system coupled to an HPLC-UV detector to determine the steady-state concentrations of DEFR (CDEFR) and Fe-(DEFR)2 (CFe-[DEFR]2) in β-thalassemia major patients (n = 8) following either once-daily or BID dosing, during which the PK parameters of the 2 dosing schedules were compared. Findings An HPLC-UV system for the analysis of blood samples following solid-phase extraction was validated. Patients who received 40 mg/kg of DEFR had higher mean CDEFR and CFe-[DEFR]2 values at all sampling times. However, concentrations of iron-DEFR complex were similar in patients who received 30 or 40 mg/kg of DEFR in the once-daily group at the 6- to 24-hour sampling times. There was no significant difference in any of the PK parameters; however, DEFR administration BID increased the mean trough levels of DEFR (183.8 [157.5] μmol/L) compared with once daily (87.7 [56.8] μmol/L), whereas all the patients had increased peak levels per individual DEFR dose when they were switched from once daily to BID (139.0 [59.8] μmol/L vs 289.2 [145.8] μmol/L, respectively). Implications Splitting the dose increased the peak levels of DEFR per unit dose in all patients and tends to increase drug exposures, but there were no significant differences in DEFR PK parameter estimates. Switching from once daily to BID may be considered for patients with an inadequate response to chelation therapy to achieve optimal drug levels. Further research is needed with a larger sample size to determine the clinical importance of the significant results due to the interindividual variability of DEFR.

原文英語
頁(從 - 到)1751-1760
頁數10
期刊Clinical Therapeutics
37
發行號8
DOIs
出版狀態已發佈 - 8月 1 2015

ASJC Scopus subject areas

  • 藥理
  • 藥學(醫學)

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