الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
 |  | from | 218 |  |  |
| | | from | 218 | | |
Abstract
Hence the objectives were:
1. To determine and validate DFX alone and in presence of OMP, VITE or SLN by using selective, sensitive, and fast high-performance liquid chromatographic (HPLC) method in plasma samples.
2. To demonstrate the application of the method by evaluating the effect of omeprazole, vitamin E and silymarin on systemic bioavailability of DFX.
3. To maximize the response to DFX and achieve the maximum therapeutic effect of deferasirox by using different regimen approaches targeting to achieve maximum peak levels of deferasirox, and subsequently reduces iron overload.
Conclusion
This work reasoned that the combined strategy of DFX with silymarin, Vitamin E or Omeprazole improved patients’ deferasirox peak levels per single dose. Silymarin and vitamin E showed highest rate of DFX absorption. DFX became relatively long-acting iron chelating agent by OMP among the four groups. This study provides many standard combinations for increasing systemic drug exposure to improve drug absorption, PK properties of DFX and reducing serum ferritin in certain patients who exhibit inadequate responses to DFX iron chelation.
This study approved in addition that omeprazole, Vitamin E or silymarin has chelating effect and also influenced the efficacy of DFX in thalassemia major. According to the current work, it seems that silymarin plus standard iron chelation may have a better result to protect organ induced iron overload. Silymarin is a safe and well-tolerated adjuvant drug without adverse effects in many clinical studies. The combination of DFX and SLN accelerated the chelation of iron, while their efficiency on further hemogram improvement appeared limited. DFX-Silymarin patients had the highest plasma concentration profile of DFX, highest AUC, and the lowest clearance from the body. These patients also had highest iron removal from the body and the lowest serum ferritin more than DFX-Vitamin E patients more than DFX- omeprazole patients compared with DFX alone. Moreover, this study achieved the correlation between pharmacokinetic finding and clinical outcomes in patients.
These findings judged that DFX plus SLN combination had the highest efficacy in iron overload. These results proved that patients with beta thalassemia who were treated with DFX concurrently to omeprazole, vitamin E and silymarin significantly benefited in terms of improvement in DFX induced liver injury through reduction of liver injury biomarkers (ALT and AST) and symptoms compared with DFX alone during the 6- months period.
These results judged the presence of a statistically significant positive correlation between DFX plasma concentration and serum creatinine in presence of omeprazole suggesting that higher drug exposure represented a potential risk for kidney function. Furthermore, the possible strategies would include alternate day use to allow a washout period or to lower the dosage in combination of DFX with omeprazole to limit the adverse effects, similar to anti-hypertensive therapy.
On the other side, Vitamin E has a renal protective effect on DFX induced nephritis by reduction the levels of serum creatinine in 40 patients. Vitamin E in patients who are excessive dependent on blood transfusion is a good treatment option for patients with extramedullary hematopoiesis. The greater DFX AUC0-24 provided lower serum ferritin levels in combined regimen rather than DFX alone suggesting that higher drug exposure represented a potential risk for kidney function.
The pharmacokinetic results were consistent with the clinical efficacy results as the in-vivo results proved that the combined regimen influenced pharmacokinetics properties of DFX followed by the highest efficiency according to serum ferritin levels.
In summary, Deferasirox, when administered combined regimens, improves iron overload and decreases DFX- related adverse effects in patients with β-thalassemia. from all the above pooled data may open a lend window of opportunity for the well-designated selected regimen approaches and offered as a second surrogate treatment line to patients who still unresponsive to DFX in beta thalassemia. These observations also might present an ideal advent of sequential clinical trials in the near future.
The strength of this study is that it is the largest and perhaps the first, prospective, randomized, study of the role of omeprazole, vitamin E and silymarin supplementation in children with β-thalassemia on the volumes of transfused packed red cells, iron overload, liver function and kidney function.