Background: Recent analysis of 19 thalassemia major patients(pts) on long-term therapy with L1, who were unsuitable for desferrioxamine therapy, showed large variability in therapeutic response to L1 as reflected in changes in hepatic iron concentration(HIC). Methods: Pts were divided into those in whom HIC was reduced to or maintained below 7mg/g.d.w.(group A ,n=7), and pts who had higher HICs during L1 therapy (group B ,n=12). We studied pharmacokinetics of L1, plasma vitamin C, drug compliance and transfusion indices, to explain the observed variability in this cohort. Results: An increase in the Vd/F of L1 was found in group B over time, with 2±0.75L/Kg and 3.16±0.81L/Kg in initial and recent measurements, respectively (p=0.006). Pts in group B had lower vitamin C levels (0.22±0.37mg/dl), compared to group A (0.74±0.52mg/dl, p=0.02). The pts in group B had started with significantly higher HICs than those in group A, despite similar ages and transfusion indices. The two groups did not differ in other parameters. Conclusions: An increase in Vd/F over time may imply a compartmental shift of iron stores, less accessed by L1. Vitamin C is an important biological co-factor affecting iron distribution. The variation in therapeutic response to L1 calls for further investigation, with special emphasis on the safety of co-administering L1 and vitamin C to iron-loaded pts.
|Number of pages
|Clinical Pharmacology and Therapeutics
|Published - 1997