Publication Date:
2006-11-16
Description:
Excess iron leads to the appearance of NTBI in the blood, which has been hypothesized to increase the risk for developing co-morbidities. LPI, one form of NTBI, is redox-active and can produce harmful reactive oxygen species. LPI is readily taken up by cells, resulting in expansion of the cellular iron pool. As LPI is produced 24 hours per day, the constant presence of an iron chelator in the plasma may help avoid accumulation of excess iron. Due to its long t½, clinically significant levels of deferasirox are present in the plasma for 24 hours following once-daily administration. This 1-year substudy has evaluated whether deferasirox treatment produced a sustained reduction in LPI. LPI, liver iron concentration (LIC; by biopsy) and serum ferritin (SF) levels over 1 year of treatment with deferasirox 20–30 mg/kg/day have been analyzed in a subgroup of 14 β-thalassemia patients from the ESCALATOR trial, all of whom had previously received DFO/deferiprone combination therapy. Blood samples for LPI and PK assessments were taken pre dose (predicted LPI daily peak) and 2 hours post dose (predicted daily LPI nadir), at baseline and following repeat dosing at weeks 4, 16, 28, 40 and 52. Efficacy and safety were assessed monthly, primarily by evaluating SF and the incidence and type of adverse events (AEs). LIC was measured at baseline and study end. The subgroup comprised 6 males and 8 females with a mean age of 17.5 years (range 12–27). Mean baseline iron parameters were: LPI 0.99 ± 0.82 μmol/L, LIC 28.6 ± 10.3 mg Fe/g dw, SF 7122 ± 3282 ng/mL. Baseline LPI levels were well correlated with LIC (R=0.66). Median deferasirox dose was 27.5 mg/kg/day. Mean steady-state deferasirox trough plasma levels at week 4 were 22.4 ± 18.5 μM (pre dose). Significant LPI reductions were observed post versus pre dose at baseline and week 4 (P
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink